Grupos Investigadores

Miembros del Grupo

Líneas de Investigación

  • Nuevos marcadores en el desarrollo de cáncer asociado a la obesidad

Palabras Clave

  • Adipoquinas
  • Cáncer
  • Fibrosis
  • Inflamación
  • Inmunidad
  • Macrófagos
  • Matriz extracelular
  • Obesidad
  • Tejido adiposo

Publicaciones Científicas desde 2018

  • Autores: Becerril Mañas, Sara (Autor de correspondencia); Álvarez-Cienfuegos Suárez, Francisco Javier; Rodríguez Murueta-Goyena, Amaia; et al.
    Revista: JOURNAL OF PHYSIOLOGY AND BIOCHEMISTRY
    ISSN: 1138-7548 Vol.80 N° 1 2024 págs. 149 - 160
    Resumen
    Bariatric surgery has become a recognized and effective procedure for treating obesity and type 2 diabetes (T2D). Our objective was to directly compare the caloric intake-independent effects of sleeve gastrectomy (SG) and single anastomosis duodenoileal bypass with SG (SADI-S) on glucose tolerance in rats with diet-induced obesity (DIO) and to elucidate the differences between bariatric surgery and caloric restriction.A total of 120 adult male Wistar rats with DIO and insulin resistance were randomly assigned to surgical (sham operation, SG, and SADI-S) and dietary (pair-feeding the amount of food eaten by animals undergoing the SG or SADI-S surgeries) interventions. Body weight and food intake were weekly monitored, and 6 weeks after interventions, fasting plasma glucose, oral glucose and insulin tolerance tests, plasma insulin, adiponectin, GIP, GLP-1, and ghrelin levels were determined.The body weight of SADI-S rats was significantly (p < 0.001) lower as compared to the sham-operated, SG, and pair-fed groups. Furthermore, SADI-S rats exhibited decreased whole body fat mass (p < 0.001), lower food efficiency rates (p < 0.001), and increased insulin sensitivity, as well as improved glucose and lipid metabolism compared to that of the SG and pair-fed rats.SADI-S was more effective than SG, or caloric restriction, in improving glycemic control and metabolic profile, with a higher remission of insulin resistance as well as long-term weight loss.
  • Autores: López-Alcalá, J.; Gordon, A. (Autor de correspondencia); Trávez, A.; et al.
    Revista: JOURNAL OF BIOMEDICAL SCIENCE
    ISSN: 1021-7770 Vol.31 N° 2 2024
    Resumen
    BackgroundExcessive lipid accumulation in the adipose tissue in obesity alters the endocrine and energy storage functions of adipocytes. Adipocyte lipid droplets represent key organelles coordinating lipid storage and mobilization in these cells. Recently, we identified the small GTPase, Rab34, in the lipid droplet proteome of adipocytes. Herein, we have characterized the distribution, intracellular transport, and potential contribution of this GTPase to adipocyte physiology and its regulation in obesity. Methods 3T3-L1 and human primary preadipocytes were differentiated in vitro and Rab34 distribution and trafficking were analyzed using markers of cellular compartments. 3T3-L1 adipocytes were transfected with expression vectors and/or Rab34 siRNA and assessed for secretory activity, lipid accumulation and expression of proteins regulating lipid metabolism. Proteomic and protein interaction analyses were employed for the identification of the Rab34 interactome. These studies were combined with functional analysis to unveil the role played by the GTPase in adipocytes, with a focus on the actions conveyed by Rab34 interacting proteins. Finally, Rab34 regulation in response to obesity was also evaluated. Results Our results show that Rab34 localizes at the Golgi apparatus in preadipocytes. During lipid droplet biogenesis, Rab34 translocates from the Golgi to endoplasmic reticulum-related compartments and then reaches the surface of adipocyte lipid droplets. Rab34 exerts distinct functions related to its intracellular location. Thus, at the Golgi, Rab34 regulates cisternae integrity as well as adiponectin trafficking and oligomerization. At the lipid droplets, this GTPase controls lipid accumulation and lipolysis through its interaction with the E1-ubiquitin ligase, UBA1, which induces the ubiquitination and proteasomal degradation of the fatty acid transporter and member of Rab34 interactome, FABP5. Finally, Rab34 levels in the adipose tissue and adipocytes are regulated in response to obesity and related pathogenic insults (i.e., fibrosis). Conclusions Rab34 plays relevant roles during adipocyte differentiation, including from the regulation of the oligomerization (i.e., biological activity) and secretion of a major adipokine with insulin-sensitizing actions, adiponectin, to lipid storage and mobilization from lipid droplets. Rab34 dysregulation in obesity may contribute to the altered adipokine secretion and lipid metabolism that characterize adipocyte dysfunction in conditions of excess adiposity.
  • Autores: Stover, P. J. (Autor de correspondencia); Field, M. S.; Andermann, M. L.; et al.
    Revista: JOURNAL OF INTERNAL MEDICINE
    ISSN: 0954-6820 Vol.294 N° 5 2023 págs. 582 - 604
    Resumen
    Eating behavior and food-related decision making are among the most complex of the motivated behaviors, and understanding the neurobiology of eating behavior, and its developmental dynamics, is critical to advancing the nutritional sciences and public health. Recent advances from both human and animal studies are revealing that individual capacity to make health-promoting food decisions varies based on biological and physiological variation in the signaling pathways that regulate the homeostatic, hedonic, and executive functions; past developmental exposures and current life-stage; the food environment; and complications of chronic disease that reinforce the obese state. Eating rate drives increased calorie intake and represents an important opportunity to lower rates of food consumption and energy intake through product reformulation. Understanding human eating behaviors and nutrition in the context of neuroscience can strengthen the evidence base from which dietary guidelines are derived and can inform policies, practices, and educational programs in a way that increases the likelihood they are adopted and effective for reducing rates of obesity and other diet-related chronic disease.
  • Autores: Tuero Ojanguren, Carlota; Becerril Mañas, Sara; Ezquerro Ezquerro, Silvia; et al.
    Revista: JOURNAL OF PHYSIOLOGY AND BIOCHEMISTRY
    ISSN: 1138-7548 Vol.79 N° 4 2023 págs. 833 - 849
    Resumen
    The underlying mechanisms for the development and progression of nonalcoholic fatty liver disease (NAFLD) are complex and multifactorial. Within the last years, experimental and clinical evidences support the role of ghrelin in the development of NAFLD. Ghrelin is a gut hormone that plays a major role in the short-term regulation of appetite and long-term regulation of adiposity. The liver constitutes a target for ghrelin, where this gut-derived peptide triggers intracellular pathways regulating lipid metabolism, inflammation, and fibrosis. Interestingly, circulating ghrelin levels are altered in patients with metabolic diseases, such as obesity, type 2 diabetes, and metabolic syndrome, which, in turn, are well-known risk factors for the pathogenesis of NAFLD. This review summarizes the molecular and cellular mechanisms involved in the hepatoprotective action of ghrelin, including the reduction of hepatocyte lipotoxicity via autophagy and fatty acid p-oxidation, mitochondrial dysfunction, endoplasmic reticulum stress and programmed cell death, the reversibility of the proinflammatory phenotype in Kupffer cells, and the inactivation of hepatic stellate cells. Together, the metabolic and inflammatory pathways regulated by ghrelin in the liver support its potential as a therapeutic target to prevent NAFLD in patients with metabolic disorders.
  • Autores: Aguas-Ayesa, M. (Autor de correspondencia); Yarnoz-Esquiroz, P.; Olazaran, L.; et al.
    Revista: REVIEWS IN ENDOCRINE AND METABOLIC DISORDERS
    ISSN: 1389-9155 Vol.24 N° 5 2023 págs. 979 - 991
    Resumen
    Bariatric surgery (BS) is the most effective long-term treatment for severe obesity. This review summarizes the main nutritional deficiencies before and after BS, as well as current dietary and supplementation recommendations to avoid them. Likewise, we have reviewed all those aspects that in recent years have been shown to be related to postoperative weight loss (WL) and its subsequent maintenance, such as hormonal changes, dietary patterns, changes in food preference, adherence to recommendations and follow-up, genetic factors and microbiota, among others. Despite all the knowledge, nutritional deficiencies and weight regain after BS are frequent. It is essential to continue studying in this field in order to establish more precise recommendations according to the individual characteristics of patients. It is also a major objective to understand more deeply the role of the factors involved in WL and its maintenance. This will allow the development of precision treatments and nutrition for patients with obesity, optimizing their benefit after BS.
  • Autores: Vazquez, L. A.; Romera, I. (Autor de correspondencia); Rubio-de Santos, M.; et al.
    Revista: DIABETES THERAPY
    ISSN: 1869-6953 Vol.14 N° 11 2023 págs. 1771 - 1784
    Resumen
    Early and intensive treatment of type 2 diabetes (T2D) has been associated with lower risk of diabetes-related complications. Control of overweight and obesity, which are strongly associated with T2D and many of its complications, is also key in the management of the disease. New therapies allow for individualised glycaemic control targets with greater safety. Thus, in patients with a higher cardiovascular and renal risk profile, current guidelines encourage early treatment with metformin together with glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and sodium-glucose co-transporter-2 inhibitors with proven cardiovascular benefit. GLP-1 RAs combine highly efficacious glucose-lowering activity with a reduced risk of hypoglycaemia. Recently, tirzepatide, a first-in-class drug that activates both glucose-dependent insulinotropic polypeptide and GLP-1 receptors, has demonstrated very high efficacy in glycated haemoglobin (HbA1c) and weight reduction in clinical trials. Tirzepatide has the potential to help people with T2D reach recommended glycaemic and weight targets (HbA1c < 7% and > 5% weight reduction) and to allow some patients to reach HbA1c measurements close to normal physiological levels and substantial weight reduction. In 2022, tirzepatide was approved by the US Food and Drug Administration and the European Medicines Agency for treatment of people with T2D and is currently in development for chronic weight management.
  • Autores: Salmón-Gómez, L.; Catalán Goñi, Victoria; Fruhbeck Martínez, Gema; et al.
    Revista: REVIEWS IN ENDOCRINE AND METABOLIC DISORDERS
    ISSN: 1389-9155 Vol.24 N° 5 2023 págs. 809 - 823
    Resumen
    Obesity is the most extended metabolic alteration worldwide increasing the risk for the development of cardiometabolic alterations such as type 2 diabetes, hypertension, and dyslipidemia. Body mass index (BMI) remains the most frequently used tool for classifying patients with obesity, but it does not accurately reflect body adiposity. In this document we review classical and new classification systems for phenotyping the obesities. Greater accuracy of and accessibility to body composition techniques at the same time as increased knowledge and use of cardiometabolic risk factors is leading to a more refined phenotyping of patients with obesity. It is time to incorporate these advances into routine clinical practice to better diagnose overweight and obesity, and to optimize the treatment of patients living with obesity.
  • Autores: Portincasa, P.; Fruhbeck Martínez, Gema (Autor de correspondencia)
    Revista: REVIEWS IN ENDOCRINE AND METABOLIC DISORDERS
    ISSN: 1389-9155 Vol.24 N° 5 2023 págs. 767 - 773
    Resumen
    In this thematic issue on phenotyping the obesities, prominent international experts offer an insightful and comprehensive collection of articles covering the current knowledge in the field. In order to actually capture all the polyhedral determinants of the diverse types of obesity, the granularity of the phenotypic information acquired must be expanded in the context of a personalized approach. Whilst the use of precision medicine has been successfully implemented in areas like cancer and other diseases, health care providers are more reluctant to embrace detailed phenotyping to guide diagnosis, treatment and prevention in obesity. Given its multiple complex layers, phenotyping necessarily needs to go beyond the multi-omics approach and incorporate all the diverse spheres that conform the reality of people living with obesity. Potential barriers, difficulties, roadblocks and opportunities together with their interaction in a syndemic context are analyzed. Plausible lacunae are also highlighted in addition to pointing to the need of redefining new conceptual frameworks. Therefore, this extraordinary collection of state-ofthe-art reviews provides useful information to both experienced clinicians and trainees as well as academics to steer clinical practice and research in the management of people living with obesity irrespective of practice setting or career stage.
  • Autores: Perdomo Zelaya, Carolina María; Cohen, R. V.; Sumithran, P.; et al.
    Revista: LANCET
    ISSN: 0140-6736 Vol.401 N° 10382 2023 págs. 1116 - 1130
    Resumen
    The goal of obesity management is to improve health. Sustained weight loss of more than 10% overall bodyweight improves many of the complications associated with obesity (eg, prevention and control of type 2 diabetes, hypertension, fatty liver disease, and obstructive sleep apnoea), as well as quality of life. Maintenance of weight loss is the major challenge of obesity management. Like all chronic diseases, managing obesity requires a long-term, multimodal approach, taking into account each individual's treatment goals, and the benefit and risk of different therapies. In conjunction with lifestyle interventions, anti-obesity medications and bariatric surgery improve the maintenance of weight loss and associated health gains. Most available anti-obesity medications act on central appetite pathways to reduce hunger and food reward. In the past 5 years, therapeutic advances have seen the development of targeted treatments for monogenic obesities and a new generation of anti-obesity medications. These highly effective anti-obesity medications are associated with weight losses of more than 10% of overall bodyweight in more than two-thirds of clinical trial participants. Long-term data on safety, efficacy, and cardiovascular outcomes are awaited. Long-term studies have shown that bariatric surgical procedures typically lead to a durable weight loss of 25% and rapid, sustained improvements in complications of obesity, although they have not yet been compared with new-generation highly effective anti-obesity medications. Further work is required to determine optimal patient-specific treatment strategies, including combinations of lifestyle interventions, anti-obesity medications, endoscopic and bariatric surgical procedures, and to ensure equitable access to effective treatments.
  • Autores: Fruhbeck Martínez, Gema (Autor de correspondencia); Gómez Ambrosi, Javier; Ramírez, B.; et al.
    Revista: FRONTIERS IN IMMUNOLOGY
    ISSN: 1664-3224 Vol.14 2023 págs. 1138316
  • Autores: Gómez Ambrosi, Javier (Autor de correspondencia)
    Revista: NUTRIENTS
    ISSN: 2072-6643 Vol.15 N° 12 2023 págs. 2651
  • Autores: Gómez Ambrosi, Javier (Autor de correspondencia)
    Revista: CELLS
    ISSN: 2073-4409 Vol.12 N° 11 2023 págs. 1484
  • Autores: García Blasco, L. (Autor de correspondencia); Pinés Corrales, P. J.; Hanzu, F.; et al.
    Revista: ENDOCRINOLOGIA DIABETES Y NUTRICION
    ISSN: 2530-0180 Vol.70 N° 4 2023 págs. 240 - 244
    Resumen
    Introduction and aims: Previous studies have shown that there is decreasing interest in E&N among medical students. The aim of our study was to evaluate the perception of E&N among a sample of medical students. Material and methods: We surveyed 2252 students prior to taking the exam that allows access to specialised training in Spain.Results: Overall, 9.9% (222 participants) would probably choose E&N. The most positive aspects in includes of the specialty are its logical pathophysiological basis (54%) and that the work is dynamic and varied (27%), while the least attractive aspects are the few interventional techniques. The parts of the specialty that most attract students are hypothalamic --pituitary disease and diabetes mellitus. Conclusions: The proportion of candidates who want to study E&N as their first choice is ade-quate in relation to the number of places available.
  • Autores: Zapata Cardenas, Juana Karina; Azcona San Julián, María Cristina; Catalán Goñi, Victoria; et al.
    Revista: CARDIOVASCULAR DIABETOLOGY
    ISSN: 1475-2840 Vol.22 N° 1 2023 págs. 240
    Resumen
    ObjectiveTo assess how inaccurately the body mass index (BMI) is used to diagnose obesity compared to body fat percentage (BF%) measurement and to compare the cardiometabolic risk in children and adolescents with or without obesity according to BMI but with a similar BF%.MethodsA retrospective cross-sectional investigation was conducted including 553 (378 females/175 males) white children and adolescents aged 6-17 years, 197 with normal weight (NW), 144 with overweight (OW) and 212 with obesity (OB) according to BMI. In addition to BMI, BF% measured by air displacement plethysmography, as well as markers of cardiometabolic risk had been determined in the existing cohort.ResultsWe found that 7% of subjects considered as NW and 62% of children and adolescents classified as OW according to BMI presented a BF% within the obesity range. Children and adolescents without obesity by the BMI criterion but with obesity by BF% exhibited higher blood pressure and C-reactive protein (CRP) in boys, and higher blood pressure, glucose, uric acid, CRP and white blood cells count, as well as reduced HDL-cholesterol, in girls, similar to those with obesity by BMI and BF%. Importantly, both groups of subjects with obesity by BF% showed a similarly altered glucose homeostasis after an OGTT as compared to their NW counterparts.ConclusionsResults from the present study suggest increased cardiometabolic risk factors in children and adolescents without obesity according to BMI but with obesity based on BF%. Being aware of the difficulty in determining body composition in everyday clinical practice, our data show that its inclusion could yield clinically useful information both for the diagnosis and treatment of overweight and obesity.
  • Autores: Becerril Mañas, Sara; Rodríguez Murueta-Goyena, Amaia; Catalán Goñi, Victoria; et al.
    Revista: NUTRIENTS
    ISSN: 2072-6643 Vol.15 N° 1 2023 págs. 73
    Resumen
    Biological sex and aging impact obesity development and type 2 diabetes, changing the secretion of leptin and adiponectin. The balance between these factors has been propounded as a reliable biomarker of adipose tissue dysfunction. Our proposal was to study sexual differences and aging on the adiponectin/leptin (Adpn/Lep) ratio in order to acquire a broader view of the impact of consuming an high-fat diet (HFD) on energy metabolism according to sex and age. Male and female C57BL/6J mice were fed a normal chow diet or an HFD for 12 or 32 weeks (n = 7-10 per group) and evolution of body weight, food intake and metabolic profile were registered. The HFD triggered an increase in body weight (p < 0.001), body weight gain (p < 0.01) and adiposity index (p < 0.01) in both sexes at 32 weeks of age, but female mice fed the HFD exhibited these changes to a significantly lower extent than males. Aged female mice showed an increase (p < 0.01) in the Adpn/Lep ratio, which was negatively correlated with body weight gain, changes in different fat depots and insulin resistance. Females were more metabolically protected from obesity development and its related comorbidities than males regardless of age, making the Adpn/Lep ratio a relevant factor for body composition and glucose metabolism.
  • Autores: Ortiz, A.; Quiroga, B. (Autor de correspondencia); Díez Martínez, Domingo Francisco Javier; et al.
    Revista: NEFROLOGIA
    ISSN: 2013-2514 Vol.43 N° 2 2023 págs. 245 - 250
    Resumen
    The 2021 guidelines on the prevention of vascular disease (VD) in clinical practice published by the European Society of Cardiology (ESC) and supported by 13 other European scientific societies recognize the key role of screening for chronic kidney disease (CKD) in the prevention of VD. Vascular risk in CKD is categorized based on measurements of estimated glomerular filtration rate (eGFR) and urine albumin to creatinine ratio (ACR). Thus, moderate CKD is associated with a high vascular risk and severe CKD with a very high vascular risk requiring therapeutic action, and there is no need to apply other vascular risk scores when vascular risk is already very high due to CKD. Moreover, the ESC indicates that vascular risk assessment and the subsequent decision algorithm should start with measurement of eGFR and ACR. To optimize the implementation of the ESC 2021 guidelines on the prevention of CVD in Spain, we consider that: 1) Urine testing for albuminuria using ACR should be part of the clinical routine at the same level as blood glucose, cholesterolemia, and GFR estimation when these are used to make decisions on CVD risk. 2) Spanish public and private health services should have the necessary means and resources to optimally implement the ESC 2021 guidelines for the prevention of CVD in Spain, including ACR testing.
  • Autores: Christou, G. A.; Andriopoulou, C. E.; Liakopoulou, A.; et al.
    Revista: HORMONES-INTERNATIONAL JOURNAL OF ENDOCRINOLOGY AND METABOLISM
    ISSN: 1109-3099 Vol.22 N° 2 2023 págs. 321 - 330
    Resumen
    PurposeAdipokines produced by adipose tissue have been found to be involved in the pathophysiology of metabolic and cardiovascular diseases. We aimed to investigate the relationships of resistin, retinol-binding protein 4 (RBP4) and adiponectin produced by epicardial adipose tissue with coronary artery disease (CAD) and cardiac structure and function.MethodsForty-one non-diabetic males scheduled for cardiothoracic surgery were examined. Anthropometric measurements, echocardiography, coronary angiography, and blood analysis were performed preoperatively. We measured the serum levels of resistin, RBP4, and adiponectin and their mRNA expression in thoracic subcutaneous adipose tissue and two epicardial adipose tissue samples, one close to left anterior descending artery (LAD) (resistin-LAD, RBP4-LAD, adiponectin-LAD), and another close to the right coronary artery (RCA) (resistin-RCA, RBP4-RCA, adiponectin-RCA).ResultsLeft ventricular (LV) ejection fraction correlated negatively with adiponectin-LAD (rho = - 0.390, p = 0.025). The ratio of early to late diastolic transmitral flow velocity, as an index of LV diastolic function, correlated negatively with resistin-LAD (rho = - 0.529, p = 0.024) and RBP4-LAD (rho = - 0.458, p = 0.049). There was no difference in epicardial adipose tissue mRNA expression of resistin, RBP4, and adiponectin between individuals with CAD and those without CAD. When we compared the individuals with CAD in the LAD with those without CAD in the LAD, there was no difference in resistin-LAD, RBP4-LAD, and adiponectin-LAD. There was no difference in resistin-RCA, RBP4-RCA, and adiponectin-RCA between the individuals with CAD in the RCA and those without CAD in the RCA.ConclusionElevation of epicardial adipose tissue mRNA expression of adiponectin was associated with LV systolic dysfunction, while that of both resistin and RBP4 was linked to LV diastolic dysfunction.
  • Autores: Otero, A.; Becerril Mañas, Sara; Martín Rodríguez, Marina; et al.
    Revista: FRONTIERS IN ENDOCRINOLOGY
    ISSN: 1664-2392 Vol.14 2023 págs. 1185456
    Resumen
    Introduction: Obesity contributes to ectopic fat deposition in non-adipose organs, including the pancreas. Pancreas steatosis associates with inflammation and beta-cell dysfunction, contributing to the onset of insulin resistance and type 2 diabetes. An improvement of pancreatic steatosis and indices of insulin resistance is observed following bariatric surgery, but the underlying mechanisms remain unknown. We sought to analyze whether guanylin (GUCA2A) and uroguanylin (GUCA2B), two gut hormones involved in the regulation of satiety, food preference and adiposity, are involved in the amelioration of pancreas fat accumulation after bariatric surgery. Methods: Pancreas steatosis, inflammation, islet number and area were measured in male Wistar rats with diet-induced obesity (n=125) subjected to surgical (sham operation and sleeve gastrectomy) or dietary (pair-fed to the amount of food eaten by gastrectomized animals) interventions. The tissue distribution of guanylate cyclase C (GUCY2C) and the expression of the guanylin system were evaluated in rat pancreata by real-time PCR, Western-blot and immunohistochemistry. The effect of guanylin and uroguanylin on factors involved in insulin secretion and lipogenesis was determined in vitro in RIN-m5F beta-cells exposed to lipotoxic conditions. Results: Sleeve gastrectomy reduced pancreas steatosis and inflammation and improved insulin sensitivity and synthesis. An upregulation of GUCA2A and GUCY2C, but not GUCA2B, was observed in pancreata from rats with dietinduced obesity one month after sleeve gastrectomy. Interestingly, both guanylin and uroguanylin diminished the lipotoxicity in palmitate-treated RIN-m5F beta-cells, evidenced by lower steatosis and downregulated lipogenic factors Srebf1, Mogat2 and Dgat1. Both guanylin peptides reduced insulin synthesis (Ins1 and Ins2) and release from RIN-m5F beta-cells, but only guanylin upregulated Wnt4, a factor that controls beta-cell proliferation and function. Discussion: Together, sleeve gastrectomy reduced pancreatic steatosis and improved beta-cell function. Several mechanisms, including the modulation of inflammation and lipogenesis as well as the upregulation of GUCA2A in the pancreas, might explain this beneficial effect of bariatric surgery.
  • Autores: Fruhbeck Martínez, Gema; Méndez-Giménez, L.; Becerril Mañas, Sara; et al.
    Revista: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
    ISSN: 1422-0067 Vol.24 N° 4 2023 págs. 3412
    Resumen
    Glycerol is a key metabolite for lipid accumulation in insulin-sensitive tissues. We examined the role of aquaporin-7 (AQP7), the main glycerol channel in adipocytes, in the improvement of brown adipose tissue (BAT) whitening, a process whereby brown adipocytes differentiate into white like unilocular cells, after cold exposure or bariatric surgery in male Wistar rats with diet-induced obesity (DIO) (n = 229). DIO promoted BAT whitening, evidenced by increased BAT hypertrophy, steatosis and upregulation of the lipogenic factors Pparg2 , Mogat2 and Dgat1. AQP7 was detected in BAT capillary endothelial cells and brown adipocytes, and its expression was upregulated by DIO. Interestingly, AQP7 gene and protein expressions were downregulated after cold exposure (4( ?)C) for 1 week or one month after sleeve gastrectomy in parallel to the improvement of BAT whitening. Moreover, Aqp7 mRNA expression was positively associated with transcripts of the lipogenic factors Pparg2 , Mogat2 and Dgat1 and regulated by lipogenic (ghrelin) and lipolytic (isoproterenol and leptin) signals. Together, the upregulation of AQP7 in DIO might contribute to glycerol influx used for triacylglycerol synthesis in brown adipocytes, and hence, BAT whitening. This process is reversible by cold exposure and bariatric surgery, thereby suggesting the potential of targeting BAT AQP7 as an anti-obesity therapy.
  • Autores: Fernandez-Saez, E. M.; Losarcos, M.; Becerril Mañas, Sara; et al.
    Revista: METABOLISM-CLINICAL AND EXPERIMENTAL
    ISSN: 0026-0495 Vol.147 2023 págs. 155663
    Resumen
    Background: The biological mediators supporting the resolution of liver steatosis, inflammation and fibrosis after bariatric surgery in patients with obesity and NAFLD remain unclear. We sought to analyze whether uroguanylin and guanylin, two gut hormones involved in the regulation of satiety, food preference and adiposity, are involved in the amelioration of obesity-associated NAFLD after bariatric surgery. Methods: Proguanylin (GUCA2A) and prouroguanylin (GUCA2B) were measured in 214 participants undergoing bariatric surgery with biopsy-proven NAFLD diagnosis. Pathways involved in lipid metabolism, mitochondrial network and fibrogenesis were evaluated in liver biopsies (n = 137). The effect of guanylin and uroguanylin on these metabolic functions was assessed in HepG2 hepatocytes and LX-2 hepatic stellate cells (HSC) under lipotoxic and profibrogenic conditions.Results: Plasma and hepatic expression of GUCA2B were decreased in obesity-associated NAFLD. Both GUCA2A and GUCA2B levels were increased after sleeve gastrectomy and Roux-en-Y gastric bypass in parallel to the improved liver function. The liver of patients with type 2 diabetes showed impaired mitochondrial & beta;-oxidation, biogenesis, dynamics as well as increased fibrosis. Uroguanylin diminished the lipotoxicity in palmitate-treated HepG2 hepatocytes, evidenced by decresased steatosis and lipogenic factors, as well as increased mitochondrial network expression, AMPK-induced & beta;-oxidation and oxygen consumption rate. Additionally, uroguanylin, but not guanylin, reversed HSC myofibroblast transdifferentiation as well as fibrogenesis after TGF-& beta;1 stimulation.Conclusions: Uroguanylin constitutes a protective factor against lipotoxicity, mitochondrial dysfunction and fibrosis. Increased GUCA2B levels might contribute to improve liver injury in patients with obesity-associated NAFLD after bariatric surgery.
  • Autores: Minambres, I.; de Hollanda, A. (Autor de correspondencia); Vilarrasa, N.; et al.
    Revista: ENDOCRINOLOGIA DIABETES Y NUTRICION
    ISSN: 2530-0180 Vol.70 N° Supl. 1 2023 págs. 110 - 115
  • Autores: Pines-Corrales, P. J. (Autor de correspondencia); Hanzu, F. A.; Casan-Fernandez, R.; et al.
    Revista: ENDOCRINOLOGIA DIABETES Y NUTRICION
    ISSN: 2530-0180 Vol.70 N° Supl. 3 2023 págs. 36 - 49
    Resumen
    Objectives: Advances in endocrinology and nutrition (E&N) and the importance of its associated disorders require that its teaching within the medical degree meets adequate standards of quality and homogeneity Our objective was to expand the data on E&N undergraduate teaching in Spain.Methods: We designed an observational, cross-sectional web-based study addressed to the coordinators of E&N teaching at the 42 faculties of medicine that had taught the subject during the 2020-2021 academic year.Results: One in three faculties had a professor who was an E&N specialist, but less than half had a full professor of E&N. There is great variability in teaching programmes, although most of them dedicate 6 ECTS credits to the subject. Over two-thirds of the faculties maintain theoretical lessons with over 50 students per class. Most programmes dedicate between four and six hours to hypothalamic pituitary disorders, thyroid diseases and adrenal gland disorders. However, there is great variability in the time dedicated to diabetes and nutrition. In one-third of the faculties, students are not required to do a rotation in the E&N department. Teachers at the universities widely participate in undergraduate/master's students' final projects and master's degree studies.Conclusions: The E&N specialty maintains a good position within universities, but there is still great heterogeneity in the teaching structure of the subject.(
  • Autores: Gonzalez-Rellan, M. J.; Parracho, T.; Heras, V.; et al.
    Revista: MOLECULAR METABOLISM
    ISSN: 2212-8778 Vol.75 2023 págs. 101776
    Resumen
    Objective: O-GlcNAcylation is a post-translational modification that directly couples the processes of nutrient sensing, metabolism, and signal transduction, affecting protein function and localization, since the O-linked N-acetylglucosamine moiety comes directly from the metabolism of glucose, lipids, and amino acids. The addition and removal of O-GlcNAc of target proteins are mediated by two highly conserved enzymes: O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) and O-GlcNAcase (OGA), respectively. Deregulation of O-GlcNAcylation has been reported to be associated with various human diseases such as cancer, diabetes, and cardiovascular diseases. The contribution of deregulated O-GlcNAcylation to the progression and pathogenesis of NAFLD remains intriguing, and a better understanding of its roles in this pathophysiological context is required to uncover novel avenues for therapeutic intervention. By using a translational approach, our aim is to describe the role of OGT and O-GlcNAcylation in the pathogenesis of NAFLD. Methods: We used primary mouse hepatocytes, human hepatic cell lines and in vivo mouse models of steatohepatitis to manipulate O-GlcNAc transferase (OGT). We also studied OGT and O-GlcNAcylation in liver samples from different cohorts of people with NAFLD. Results: O-GlcNAcylation was upregulated in the liver of people and animal models with steatohepatitis. Downregulation of OGT in NAFLD-hepatocytes improved diet-induced liver injury in both in vivo and in vitro models. Proteomics studies revealed that mitochondrial proteins were hyper-O-GlcNAcylated in the liver of mice with steatohepatitis. Inhibition of OGT is able to restore mitochondrial oxidation and decrease hepatic lipid content in in vitro and in vivo models of NAFLD. Conclusions: These results demonstrate that deregulated hyper-O-GlcNAcylation favors NAFLD progression by reducing mitochondrial oxidation and promoting hepatic lipid accumulation.
  • Autores: Fernández González, Secundino (Autor de correspondencia); Prieto Matos, Carlos; Ferrán de la Cierva, Sol; et al.
    Revista: OTOLARYNGOLOGY CASE REPORTS
    ISSN: 2468-5488 Vol.26 2023 págs. 100501
  • Autores: Valero-Rubira, I.; Castillo, A. M.; Burrell Bustos, María Ángela; et al.
    Revista: FRONTIERS IN PLANT SCIENCE
    ISSN: 1664-462X Vol.13 2023 págs. 1058421
    Resumen
    Reprogramming of microspores development towards embryogenesis mediated by stress treatment constitutes the basis of doubled haploid production. Recently, compounds that alter histone post-translational modifications (PTMs) have been reported to enhance microspore embryogenesis (ME), by altering histones acetylation or methylation. However, epigenetic mechanisms underlying ME induction efficiency are poorly understood. In this study, the epigenetic dynamics and the expression of genes associated with histone PTMs and ME induction were studied in two bread wheat cultivars with different ME response. Microspores isolated at 0, 3 and 5 days, treated with 0.7M mannitol (MAN) and 0.7M mannitol plus 0.4 mu M trichostatin A (TSA), which induced ME more efficiently, were analyzed. An additional control of gametophytic development was included. Microspores epigenetic state at the onset of ME induction was distinctive between cultivars by the ratio of H3 variants and their acetylated forms, the localization and percentage of labeled microspores with H3K9ac, H4K5ac, H4K16ac, H3K9me2 and H3K27me3, and the expression of genes related to pollen development. These results indicated that microspores of the high responding cultivar could be at a less advanced stage in pollen development. MAN and TSA resulted in a hyperacetylation of H3.2, with a greater effect of TSA. Histone PTMs were differentially affected by both treatments, with acetylation being most concerned. The effect of TSA was observed in the H4K5ac localization pattern at 3dT in the mid-low responding cultivar. Three gene networks linked to ME response were identified. TaHDT1, TaHAG2, TaYAO, TaNFD6-A, TabZIPF1 and TaAGO802-B, associated with pollen development, were down-regulated. TaHDA15, TaHAG3, TaHAM, TaYUC11D, Ta-2B-LBD16 TaMS1 and TaDRM3 constituted a network implicated in morphological changes by auxin signaling and cell wall modification up-regulated at 3dT. The last network included TaHDA18, TaHAC1, TaHAC4, TaABI5, TaATG18fD, TaSDG1a-7A and was related to ABA and ethylene hormone signaling pathways, DNA methylation and autophagy processes, reaching the highest expression at 5dT. The results indicated that TSA mainly modified the regulation of genes related to pollen and auxin signaling. This study represents a breakthrough in identifying the epigenetic dynamics and the molecular mechanisms governing ME induction efficiency, with relevance to recalcitrant wheat genotypes and other crops.
  • Autores: Oliveras-Canellas, N.; Moreno-Navarrete, J. M.; Lorenzo, P. M.; et al.
    Revista: JOURNAL OF CLINICAL ENDOCRINOLOGY AND METABOLISM
    ISSN: 0021-972X Vol.109 N° 1 2023 págs. e145 - e154
    Resumen
    Context Climate change and global warming have been hypothesized to influence the increased prevalence of obesity worldwide. However, the evidence is scarce. Objective We aimed to investigate how outside temperature might affect adipose tissue physiology and metabolic traits. Methods The expression of genes involved in thermogenesis/browning and adipogenesis were evaluated (through quantitative polymerase chain reaction) in the subcutaneous adipose tissue (SAT) from 1083 individuals recruited in 5 different regions of Spain (3 in the North and 2 in the South). Plasma biochemical variables and adiponectin (enzyme-linked immunosorbent assay) were collected through standardized protocols. Mean environmental outdoor temperatures were obtained from the National Agency of Meteorology. Univariate, multivariate, and artificial intelligence analyses (Boruta algorithm) were performed. Results The SAT expression of genes associated with browning (UCP1, PRDM16, and CIDEA) and ADIPOQ were significantly and negatively associated with minimum, average, and maximum temperatures. The latter temperatures were also negatively associated with the expression of genes involved in adipogenesis (FASN, SLC2A4, and PLIN1). Decreased SAT expression of UCP1 and ADIPOQ messenger RNA and circulating adiponectin were observed with increasing temperatures in all individuals as a whole and within participants with obesity in univariate, multivariate, and artificial intelligence analyses. The differences remained statistically significant in individuals without type 2 diabetes and in samples collected during winter. Conclusion Decreased adipose tissue expression of genes involved in browning and adiponectin with increased environmental temperatures were observed. Given the North-South gradient of obesity prevalence in these same regions, the present observations could have implications for the relationship of the obesity pandemic with global warming.
  • Autores: Gonzalez-Rellan, M. J.; Fernández, U.; Parracho, T.; et al.
    Revista: CELL METABOLISM
    ISSN: 1550-4131 Vol.35 N° 9 2023 págs. 1630 - 1645
    Resumen
    Neddylation is a post-translational mechanism that adds a ubiquitin-like protein, namely neural precursor cell expressed developmentally downregulated protein 8 (NEDD8). Here, we show that neddylation in mouse liver is modulated by nutrient availability. Inhibition of neddylation in mouse liver reduces gluconeogenic capacity and the hyperglycemic actions of counter-regulatory hormones. Furthermore, people with type 2 diabetes display elevated hepatic neddylation levels. Mechanistically, fasting or caloric restriction of mice leads to neddylation of phosphoenolpyruvate carboxykinase 1 (PCK1) at three lysine residues-K278, K342, and K387. We find that mutating the three PCK1 lysines that are neddylated reduces their gluconeogenic activity rate. Molecular dynamics simulations show that neddylation of PCK1 could re-position two loops surrounding the catalytic center into an open configuration, rendering the catalytic center more accessible. Our study reveals that neddylation of PCK1 provides a finely tuned mechanism of controlling glucose metabolism by linking whole nutrient availability to metabolic homeostasis.
  • Autores: Reyes-Garcia, R. (Autor de correspondencia); Moreno-Perez, O.; Bellido, V.; et al.
    Revista: ENDOCRINOLOGIA DIABETES Y NUTRICION
    ISSN: 2530-0180 Vol.70 N° Supl. 1 2023 págs. 95 - 102
    Resumen
    Objective: To provide practical recommendations for the comprehensive approach of peoplewith type 2 diabetes according to evidence-based medicine. Participants: Members of the Diabetes Knowledge Area of the Spanish Society of Endocrinologyand Nutrition. Methods: The recommendations were formulated according to the degrees of evidence of theStandards of Medical Care in Diabetes-2022. After reviewing the available evidence and formulating recommendations by the authors of each section, several rounds of comments weredeveloped incorporating the contributions and voting on controversial points. Finally, the finaldocument was sent to the rest of the members of the area for review and incorporation ofcontributions, to finally carry out the same process with the members of the Spanish Society ofEndocrinology and Nutrition Board of Directors. Conclusions: The document establishes practical recommendations based on the latest available evidence for the management of people with type 2 diabetes.
  • Autores: Nokes, B. (Autor de correspondencia); Baptista Jardín, Peter Michael; Martínez Ruiz de Apodaca, P.; et al.
    Revista: SLEEP AND BREATHING
    ISSN: 1520-9512 Vol.27 N° 2 2023 págs. 527 - 534
    Resumen
    Introduction: Obstructive sleep apnea (OSA) is a common disorder with major neurocognitive and cardiovascular sequelae. The treatment of symptomatic patients with mild OSA remains controversial given that adherence to positive airway pressure (PAP) has historically been suboptimal. With this notion in mind, we assessed a daily transoral neuromuscular electrical stimulation (NMES) device for individuals with mild OSA. Methods: The sample represents a subset of participants with a baseline AHI 5-14.9 events/hour, drawn from a parent study which also included participants with primary snoring. Outcome measures for the current study included changes in apnea-hypopnea index (AHI), Epworth Sleepiness Scale (ESS), Pittsburgh Sleep Quality Index (PSQI) and snoring levels before and after use of the NMES. RESULTS: Among 65 participants (68% men) with median age of 49 years (range 24 to 79) and median BMI of 27.7 kg/m2 (range 20 to 34), the NMES device was used daily for 6 weeks. We observed a significant improvement in the AHI from 10.2 to 6.8 events/hour among all participants and from 10.4 to 5.0 events/h among responders. Statistically significant improvements in the ESS, PSQI, objectively measured snoring, and bed partner-reported snoring were observed. Adherence among all participants was 85%. Discussion: This NMES device has the benefit of being a treatment modality of daytime therapy which confers a high level of tolerability and patient acceptance. It alleviates the need for an in situ device during sleep and leads to improvements in OSA severity, snoring, and subjective sleep metrics, potentially crucial in mild OSA. Further studies are needed to define which individuals may benefit most from the device across the wider spectrum of OSA severity and assess long-term therapeutic outcomes. Trial registration: ClinicalTrials.gov Identifier: NCT03829956.
  • Autores: Aguas-Ayesa, M.; Yárnoz-Esquiroz, P.; Olazarán, L.; et al.
    Revista: NUTRIENTS
    ISSN: 2072-6643 Vol.15 N° 22 2023 págs. 4824
    Resumen
    Unhealthy dietary habits and sedentarism coexist with a rising incidence of excess weight and associated comorbidities. We aimed to analyze the dietary and drinking patterns of patients with excess weight, their main characteristics, plausible gender differences and impact on cardiometabolic risk factors, with a particular focus on the potential contribution of beer consumption. Data from 200 consecutive volunteers (38 +/- 12 years; 72% females) living with overweight or class I obesity attending the obesity unit to lose weight were studied. Food frequency questionnaires and 24 h recalls were used. Reduced-rank regression (RRR) analysis was applied to identify dietary patterns (DPs). Anthropometry, total and visceral fat, indirect calorimetry, physical activity level, comorbidities and circulating cardiometabolic risk factors were assessed. Study participants showed high waist circumference, adiposity, insulin resistance, dyslipidemia, pro-inflammatory adipokines and low anti-inflammatory factors like adiponectin and interleukin-4. A low-fiber, high-fat, energy-dense DP was observed. BMI showed a statistically significant (p < 0.05) correlation with energy density (r = 0.80) as well as percentage of energy derived from fat (r = 0.61). Excess weight was associated with a DP low in vegetables, legumes and whole grains at the same time as being high in sweets, sugar-sweetened beverages, fat spreads, and processed meats. RRR analysis identified a DP characterized by high energy density and saturated fat exhibiting negative loadings (>-0.30) for green leafy vegetables, legumes, and fruits at the same time as showing positive factor loadings (>0.30) for processed foods, fat spreads, sugar-sweetened beverages, and sweets. Interestingly, for both women and men, wine represented globally the main source of total alcohol intake (p < 0.05) as compared to beer and distillates. Beer consumption cannot be blamed as the main culprit of excess weight. Capturing the DP provides more clinically relevant and useful information. The focus on consumption of single nutrients does not resemble real-world intake behaviors.
  • Autores: Perdomo Zelaya, Carolina María; Avilés Olmos, Iciar; Dicker, D.; et al.
    Revista: REVIEWS IN ENDOCRINE AND METABOLIC DISORDERS
    ISSN: 1389-9155 Vol.24 N° 5 2023 págs. 795 - 807
    Resumen
    Obesity is a complex disease that relapses frequently and associates with multiple complications that comprise a worldwide health priority because of its rising prevalence and association with numerous complications, including metabolic disorders, mechanic pathologies, and cancer, among others. Noteworthy, excess adiposity is accompanied by chronic inflammation, oxidative stress, insulin resistance, and subsequent organ dysfunction. This dysfunctional adipose tissue is initially stored in the visceral depot, overflowing subsequently to produce lipotoxicity in ectopic depots like liver, heart, muscle, and pancreas, among others. People living with obesity need a diagnostic approach that considers an exhaustive pathophysiology and complications assessment. Thus, it is essential to warrant a holistic diagnosis and management that guarantees an adequate health status, and quality of life. The present review summarizes the different complications associated with obesity, at the same time, we aim to fostering a novel framework that enhances a patient-centered approach to obesity management in the precision medicine era.
  • Autores: González-Rellán, M. J.; Novoa, E.; da Silva Lima, N.; et al.
    Revista: GUT
    ISSN: 0017-5749 Vol.72 N° 3 2023 págs. 472 - 483
    Resumen
    Objective p63 is a transcription factor within the p53 protein family that has key roles in development, differentiation and prevention of senescence, but its metabolic actions remain largely unknown. Herein, we investigated the physiological role of p63 in glucose metabolism. Design We used cell lines and mouse models to genetically manipulate p63 in hepatocytes. We also measured p63 in the liver of patients with obesity with or without type 2 diabetes (T2D). Results We show that hepatic p63 expression is reduced on fasting. Mice lacking the specific isoform TAp63 in the liver (p63LKO) display higher postprandial and pyruvate-induced glucose excursions. These mice have elevated SIRT1 levels, while SIRT1 knockdown in p63LKO mice normalises glycaemia. Overexpression of TAp63 in wild-type mice reduces postprandial, pyruvate-induced blood glucose and SIRT1 levels. Studies carried out in hepatocyte cell lines show that TAp63 regulates SIRT1 promoter by repressing its transcriptional activation. TAp63 also mediates the inhibitory effect of insulin on hepatic glucose production, as silencing TAp63 impairs insulin sensitivity. Finally, protein levels of TAp63 are reduced in obese persons with T2D and are negatively correlated with fasting glucose and homeostasis model assessment index. Conclusions. These results demonstrate that p63 physiologically regulates glucose homeostasis.
  • Autores: Llorente Ortega, Marcos; Polo, R.; Chiva San Román, Santiago; et al.
    Revista: ACTAS UROLÓGICAS ESPAÑOLAS (ENGLISH ED.)
    ISSN: 2173-5786 Vol.47 N° 4 2023 págs. 236 - 243
    Resumen
    Introduction: Simulation in medicine has developed a lot in the last few decades. There is a broad range of simulators available, above all for training in surgical procedures. Endourology can benefit much from simulation because the minimally-invasive procedures of endourology frequently have long learning curves, which can be reduced by training with simulators. Materials and methods: A low-fidelity simulator was designed for practicing endourology techniques that use cystoscopy. The process of validation involved 5 experts and 19 non-experts. Experts comprised medical professionals working in a department of urology who had performed at least 100 flexible cystoscopy procedures. Non-experts were residents in internal medicine without experience in any type of endoscopy. Information about face and content validity was collected by means of Likert scales from 1 to 5. To evaluate construct validity, we measured the time to complete two tasks, for which the procedure was evaluated by means of the OSATS global evaluation scale. Results: New simulator was successfully built according to its design. For all evaluated aspects of construct validity, there was a significant difference (p < 0.05) between the group of experts and the group of non-experts. Content validity was scored 4.66 (standard deviation ±0.56) by the experts and 4.41 (±0.71) by the non-experts. In the face validity questionnaire, the average score was 4.14 (±0.94), the question receiving the highest score: 4.6 (±0.84) concerned immersion in the procedure. Conclusion: The simulator presented is valid both for training up new urologists in endourology technique and for experts seeking to perfect their skills.
  • Autores: Ezquerro Ezquerro, Silvia; Tuero Ojanguren, Carlota; Becerril Mañas, Sara; et al.
    Revista: EUROPEAN JOURNAL OF ENDOCRINOLOGY
    ISSN: 0804-4643 Vol.188 N° 7 2023 págs. 564 - 577
    Resumen
    Background Growing evidence suggests the key role of ghrelin in the onset and progression of nonalcoholic fatty liver disease (NAFLD). The potential participation of ghrelin and the ghrelin receptor antagonist, LEAP-2, in the onset of liver fibrosis in patients with severe obesity and NAFLD through the regulation of TGF-& beta;1-induced hepatic stellate cell (HSC) activation was investigated. Methods Circulating (n = 179) and hepatic expression (n = 95) of ghrelin and LEAP-2 were measured in patients with severe obesity and available liver pathology analysis undergoing Roux-en-Y gastric bypass (RYGB). The effect of ghrelin isoforms and LEAP-2 on TGF-& beta;1-induced HSC activation, fibrogenic response, and contractile properties was evaluated in vitro in human LX-2 cells. Results Plasma and hepatic ghrelin were negatively associated, while LEAP-2 exhibited a positive association with liver fibrosis in patients with obesity and NAFLD. Six months after RYGB, hepatic function was improved and, although acylated ghrelin and LEAP-2 concentrations remained unchanged, both hormones were inversely related to post-surgical levels of profibrogenic factors TGF-& beta;1 and TIMP-1. Acylated ghrelin treatment reversed TGF-& beta;1-induced myofibroblast-like phenotype, collagen contractile properties, and the upregulation of factors involved in HSC activation and fibrogenesis via PI3K/Akt/mTOR pathway. Moreover, acylated ghrelin inhibited the mild HSC activation induced by LEAP-2. Conclusions Ghrelin is an anti-fibrogenic factor blocking HSC activation induced by the most potent fibrogenic cytokine, TGF-& beta;1, and LEAP-2. The imbalance between acylated ghrelin and ghrelin receptor antagonist LEAP-2 might contribute to maintain liver fibrosis in patients with obesity and NAFLD.
  • Autores: Mentxaka, A.; Gómez Ambrosi, Javier; Neira, G.; et al.
    Revista: CANCERS
    ISSN: 2072-6694 Vol.15 N° 4 2023 págs. 1038
    Resumen
    Simple Summary Netrin-1 (NTN-1) regulates obesity-associated low-grade inflammation, being also involved in the control of cell migration and proliferation. We aim to study whether excess visceral adipose tissue in patients with obesity and colon cancer is associated with increased NTN1 and the expression levels of its main receptors, promoting an inflammatory microenvironment that favours colon cancer development. Increased expression levels of NTN1 and its receptor NEO1 in the visceral adipose tissue from patients with obesity and colon cancer together with elevated DCC and UNC5B mRNA levels in patients with colon cancer were found. Moreover, the treatment of colorectal cancer cells with NTN-1 and with the adipocyte-derived secretome obtained from patients with obesity increased the migration of colorectal cancer cells. These results suggest that NTN-1 plays an important role in obesity-associated colon cancer development. Netrin (NTN)-1, an extracellular matrix protein with a crucial role in inflammation, is dysregulated during obesity (OB) and influences colon cancer (CC) progression. To decipher the mechanisms underlying CC development during obesity, we examined the expression of NTN1 and its receptors in the visceral adipose tissue (VAT) of 74 (25 normal weight (NW)) (16 with CC) and 49 patients with OB (12 with CC). We also evaluated the effect of caloric restriction (CR) on the gene expression levels of Ntn1 and its receptors in the colon from a rat model fed a normal diet. The impact of adipocyte-conditioned media (ACM) from patients with OB and NTN-1 was assessed on the expression levels of neogenin 1(NEO1), deleted in colorectal carcinomas (DCC) and uncoordinated-5 homolog B (UNC5B) in Caco-2 and HT-29 human colorectal cell lines, as well as on Caco-2 cell migration. Increased NTN1 and NEO1 mRNA levels in VAT were due to OB (p < 0.05) and CC (p < 0.001). In addition, an upregulation in the expression levels of DCC and UNC5B in patients with CC (p < 0.01 and p < 0.05, respectively) was observed. Decreased (p < 0.01) Ntn1 levels in the colon from rats submitted to CR were found. In vitro experiments showed that ACM increased DCC (p < 0.05) and NEO1 (p < 0.01) mRNA levels in HT-29 and Caco-2 cell lines, respectively, while UNC5B decreased (p < 0.01) in HT-29. The treatment with NTN-1 increased (p < 0.05) NEO1 mRNA levels in HT-29 cells and DCC (p < 0.05) in both cell lines. Finally, we revealed a potent migratory effect of ACM and NTN-1 on Caco-2 cells. Collectively, these findings point to increased NTN-1 during OB and CC fuelling cancer progression and exerting a strong migratory effect on colon cancer cells.
  • Autores: Lujan Colas, J.; Martín Gómez, Elena; Rotellar Sastre, Fernando; et al.
    Revista: OBESITY SURGERY
    ISSN: 0960-8923 Vol.33 N° Supl. 2 2023 págs. 775
  • Autores: Cheng, A.; Sloan, L.; Carlson, A.; et al.
    Revista: DIABETES TECHNOLOGY AND THERAPEUTICS
    ISSN: 1520-9156 Vol.25 N° Supl. 2 2023 págs. A131
  • Autores: Fruhbeck Martínez, Gema (Autor de correspondencia)
    Revista: EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
    ISSN: 0014-2972 Vol.53 N° Supl. 1 2023
  • Autores: Botana, M.; Escalada San Martín, Francisco Javier; Merchante, A.; et al.
    Revista: DIABETES THERAPY
    ISSN: 1869-6953 Vol.13 N° Supl. 1 2022 págs. 5 - 17
    Resumen
    Heart failure (HF) and chronic kidney disease (CKD) are the most frequent first cardiorenal conditions in patients with type 2 diabetes (T2D), which can be exacerbated by other comorbidities, such as hypertension, dyslipidemia, and obesity. To improve their clinical outcomes, patients with T2D need to achieve and maintain glycemic targets, as well as prevent cardiorenal disease onset and progression. Several clinical trials evaluating the sodium-glucose cotransporter type 2 inhibitors (SGLT2i) dapagliflozin, empagliflozin, canagliflozin, and ertugliflozin have shown consistent risk reduction in major adverse cardiovascular events and/or hospitalization for HF, together with lower risk of kidney disease progression. The benefits associated with SGLT2i in T2D are distinct from other antihyperglycemic drugs since they have been proposed to exert pleiotropic metabolic and direct effects on the kidney and the heart. In this review, we summarize and discuss the evidence regarding the mechanisms of action, the efficacy and safety profiles, and the clinical guidelines on the use of the therapeutic class of SGLT2i, highlighting their role in cardiorenal prevention beyond glycemic control.
  • Autores: Khalil, M.; Shanmugam, H.; Abdallah, H.; et al.
    Revista: INSECTS
    ISSN: 2075-4450 Vol.14 N° 15 2022 págs. 3112
    Resumen
    The abnormal expansion of body fat paves the way for several metabolic abnormalities including overweight, obesity, and diabetes, which ultimately cluster under the umbrella of metabolic syndrome (MetS). Patients with MetS are at an increased risk of cardiovascular disease, morbidity, and mortality. The coexistence of distinct metabolic abnormalities is associated with the release of pro-inflammatory adipocytokines, as components of low-to-medium grade systemic inflammation and increased oxidative stress. Adopting healthy lifestyles, by using appropriate dietary regimens, contributes to the prevention and treatment of MetS. Metabolic abnormalities can influence the function and energetic capacity of mitochondria, as observed in many obesity-related cardio-metabolic disorders. There are preclinical studies both in cellular and animal models, as well as clinical studies, dealing with distinct nutrients of the Mediterranean diet (MD) and dysfunctional mitochondria in obesity and MetS. The term Mitochondria nutrients has been adopted in recent years, and it depicts the adequate nutrients to keep proper mitochondrial function. Different experimental models show that components of the MD, including polyphenols, plant-derived compounds, and polyunsaturated fatty acids, can improve mitochondrial metabolism, biogenesis, and antioxidant capacity. Such effects are valuable to counteract the mitochondrial dysfunction associated with obesity-related abnormalities and can represent the beneficial feature of polyphenols-enriched olive oil, vegetables, nuts, fish, and plant-based foods, as the main components of the MD. Thus, developing mitochondria-targeting nutrients and natural agents for MetS treatment and/or prevention is a logical strategy to decrease the burden of disease and medications at a later stage. In this comprehensive review, we discuss the effects of the MD and its bioactive components on improving mitochondrial structure and activity.
  • Autores: Stover, P. J. (Autor de correspondencia); Field, M. S.; Brawley, H. N.; et al.
    Revista: JOURNAL OF INTERNAL MEDICINE
    ISSN: 0954-6820 Vol.292 N° 4 2022 págs. 587 - 603
    Resumen
    Adult stem cells (SCs) represent the regenerative capacity of organisms throughout their lifespan. The maintenance of robust SC populations capable of renewing organs and physiological systems is one hallmark of healthy aging. The local environment of SCs, referred to as the niche, includes the nutritional milieu, which is essential to maintain the quantity and quality of SCs available for renewal and regeneration. There is increased recognition that SCs have unique metabolism and conditional nutrient needs compared to fully differentiated cells. However, the contribution of SC nutrition to overall human nutritional requirements is an understudied and underappreciated area of investigation. Nutrient needs vary across the lifespan and are modified by many factors including individual health, disease, physiological states including pregnancy, age, sex, and during recovery from injury. Although current nutrition guidance is generally derived for apparently healthy populations and to prevent nutritional deficiency diseases, there are increased efforts to establish nutrient-based and food-based recommendations based on reducing chronic disease. Understanding the dynamics of SC nutritional needs throughout the life span, including the role of nutrition in extending biological age by blunting biological systems decay, is fundamental to establishing food and nutrient guidance for chronic disease reduction and health maintenance. This review summarizes a 3-day symposium of the Marabou Foundation () held to examine the metabolic properties and unique nutritional needs of adult SCs and their role in healthy aging and age-related chronic disease.
  • Autores: Catalán Goñi, Victoria; Avilés Olmos, Iciar; Rodríguez Murueta-Goyena, Amaia; et al.
    Revista: NUTRIENTS
    ISSN: 2072-6643 Vol.14 N° 8 2022 págs. 1597
    Resumen
    The obesity epidemic shows no signs of abatement. Genetics and overnutrition together with a dramatic decline in physical activity are the alleged main causes for this pandemic. While they undoubtedly represent the main contributors to the obesity problem, they are not able to fully explain all cases and current trends. In this context, a body of knowledge related to exposure to as yet underappreciated obesogenic factors, which can be referred to as the "exposome", merits detailed analysis. Contrarily to the genome, the "exposome" is subject to a great dynamism and variability, which unfolds throughout the individual's lifetime. The development of precise ways of capturing the full exposure spectrum of a person is extraordinarily demanding. Data derived from epidemiological studies linking excess weight with elevated ambient temperatures, in utero, and intergenerational effects as well as epigenetics, microorganisms, microbiota, sleep curtailment, and endocrine disruptors, among others, suggests the possibility that they may work alone or synergistically as several alternative putative contributors to this global epidemic. This narrative review reports the available evidence on as yet underappreciated drivers of the obesity epidemic. Broadly based interventions are needed to better identify these drivers at the same time as stimulating reflection on the potential relevance of the "exposome" in the development and perpetuation of the obesity epidemic.
  • Autores: Portincasa, P. (Autor de correspondencia); Bonfrate, L.; Wang, D. Q. H.; et al.
    Revista: EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
    ISSN: 0014-2972 Vol.52 N° 11 2022 págs. e13846
    Resumen
    Type 2 and type 1 diabetes are common endocrine disorders with a progressively increasing incidence worldwide. These chronic, systemic diseases have multiorgan implications, and the whole gastrointestinal (GI) tract represents a frequent target in terms of symptom appearance and interdependent pathophysiological mechanisms. Metabolic alterations linked with diabetic complications, neuropathy and disrupted hormone homeostasis can lead to upper and/or lower GI symptoms in up to 75% of diabetic patients, with multifactorial involvement of the oesophagus, stomach, upper and lower intestine, and of the gallbladder. On the other hand, altered gastrointestinal motility and/or secretions are able to affect glucose and lipid homeostasis in the short and long term. Finally, diabetes has been linked with increased cancer risk at different levels of the GI tract. The presence of GI symptoms and a comprehensive assessment of GI function should be carefully considered in the management of diabetic patients to avoid further complications and to ameliorate the quality of life. Additionally, the presence of gastrointestinal dysfunction should be adequately managed to improve metabolic homeostasis, the efficacy of antidiabetic treatments and secondary prevention strategies.
  • Autores: Aliseda Jover, Daniel (Autor de correspondencia); Álvarez-Cienfuegos Suárez, Francisco Javier; Valentí Azcarate, Víctor; et al.
    Revista: ANZ JOURNAL OF SURGERY
    ISSN: 1445-1433 Vol.92 N° 3 2022 págs. 620 - 620
  • Autores: Almeida Vargas, Ana; Baixauli Fons, Jorge; Álvarez-Cienfuegos Suárez, Francisco Javier (Autor de correspondencia); et al.
    Revista: CIRUGIA ESPAÑOLA
    ISSN: 0009-739X Vol.100 N° 11 2022 págs. 736 - 738
  • Autores: Álvarez-Cienfuegos Suárez, Francisco Javier (Autor de correspondencia); Valentí Azcarate, Víctor; Rotellar Sastre, Fernando
    Revista: REVISTA ESPAÑOLA DE ENFERMEDADES DIGESTIVAS
    ISSN: 1130-0108 Vol.114 N° 2 2022 págs. 73 - 75
    Resumen
    Acute pancreatitis (AP) is the third most frequent cause of hospital admissions for digestive disorders in the US and Europe after digestive bleeding and cholelithiasis/cholecystitis. The incidence of AP ranges from 15 to 100 cases per 100,000 inhabitants per year, and has been steadily increasing in recent years. In Spain, the reported incidence is 72 patients per 100,000 inhabitants per year. The most frequent cause is biliary lithiasis (50 %-60 % of cases); fortunately, 80 % of patients have only mild symptoms¿as defined by the revised Atlanta Classification¿and progress favorably, although mortality rate is 4.2 %. Clinical guidelines explicitly indicate that laparoscopic cholecystectomy should be performed during the first 48-72 hours or at the time of hospital admission in mild cases of biliary origin.
  • Autores: Gómez Ambrosi, Javier
    Revista: NUTRIENTS
    ISSN: 2072-6643 Vol.14 N° 3 2022 págs. 421
  • Autores: Gómez Ambrosi, Javier (Autor de correspondencia); Catalán Goñi, Victoria; Fruhbeck Martínez, Gema
    Revista: EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
    ISSN: 0014-2972 Vol.52 N° 5 2022 págs. e13723
  • Autores: Escalada San Martín, Francisco Javier
    Revista: DIABETES THERAPY
    ISSN: 1869-6953 Vol.13 N° Supl. 1 2022 págs. 1 - 3
  • Autores: Gómez Ambrosi, Javier (Autor de correspondencia); Catalán Goñi, Victoria
    Revista: ANALES DEL SISTEMA SANITARIO DE NAVARRA
    ISSN: 1137-6627 Vol.41 N° 1 2022 págs. e0993
  • Autores: Donini, L. M. (Autor de correspondencia); Busetto, L.; Bischoff, S. C.; et al.
    Revista: OBESITY FACTS
    ISSN: 1662-4025 Vol.15 N° 3 2022 págs. 321 - 335
    Resumen
    Introduction: Loss of skeletal muscle mass and function (sarcopenia) is common in individuals with obesity due to metabolic changes associated with a sedentary lifestyle, adipose tissue derangements, comorbidities (acute and chronic diseases), and during the ageing process. Co-existence of excess adiposity and low muscle mass/function is referred to as sarcopenic obesity (SO), a condition increasingly recognized for its clinical and functional features that negatively influence important patient-centred outcomes. Effective prevention and treatment strategies for SO are urgently needed, but efforts are hampered by the lack of an universally established SO Definition and diagnostic criteria. Resulting inconsistencies in the literature also negatively affect the ability to define prevalence as well as clinical relevance of SO for negative health outcomes. Aims and methods: The European Society for Clinical Nutrition and Metabolism (ESPEN) and the European Association for the Study of Obesity (EASO) launched an initiative to reach expert consensus on a Definition and diagnostic criteria for SO. The jointly appointed international expert panel proposes that SO is defined as the co-existence of excess adiposity and low muscle mass/function. The diagnosis of SO should be considered in at-risk individuals who screen positive for a co-occurring elevated body mass index or waist circumference, and markers of low skeletal muscle mass and function (risk factors, clinical symptoms, or validated questionnaires). Diagnostic procedures should initially include assessment of skeletal muscle function, followed by assessment of body composition where presence of excess adiposity and low skeletal muscle mass or related body compartments confirm the diagnosis of SO. Individuals with SO should be further stratified into Stage I in the absence of clinical complications, or Stage II if cases are associated with complications linked to altered body composition or skeletal muscle dysfunction. Conclusions: ESPEN and EASO, as well as the expert international panel, advocate that the proposed SO Definition and diagnostic criteria be implemented into routine clinical practice. The panel also encourages prospective studies in addition to secondary analysis of existing datasets, to study the predictive value, treatment efficacy, and clinical impact of this SO definition.
  • Autores: Liu, Q.; Reed, M.; Zhu, H.; et al.
    Revista: GENOMICS
    ISSN: 0888-7543 Vol.114 N° 5 2022 págs. 110474
    Resumen
    Background: It has become increasingly important to identify molecular markers for accurately diagnosing prostate cancer (PCa) stages between localized PCa (LPC) and locally advanced PCa (LAPC). However, there is a lack of profiling both epigenome-wide DNA methylation and transcriptome for the same patients with PCa at different stages. This study aims to identify epitranscriptomic biomarkers screened in the periprostatic (PP) adipose tissue for predicting LPC and LAPC. Methods: We profiled gene expression and DNA methylation of 10 PCa patients' PP adipose tissue (4 LPC and 6 LAPC). Differential analysis was used to identify differentially methylated CpG sites and expressed genes. An integrative analysis of the microarray gene expression profiles and DNA methylation profiles was conducted using LASSO (least absolute shrinkage and selection operator) between each studied gene and the CpG sites in their promoter region. This epitranscriptomic signature was constructed by combining the association and differential analyses. The signature was then refined using the genetic mutation data of > 1500 primary PCa and metastasis PCa samples from 4 different studies. We determined genes that were the most significantly affected by mutations. Machine learning models were built to evaluate the classification ability of the identified signature using the gene expression profiles from three external cohorts. Results: From the LASSO-based association analysis, we identified 56 genes presenting significant anti-correlation between the expression level and the methylation level of at least one CpG site in the promoter region (p-value < 5 x 10(-8)). From the differential analysis, we detected 16,405 downregulated genes and 9485 genes containing at least one hypermethylated CpG site. We identified 30 genes that showed anti-correlation, down-regulation and hyper-methylation simultaneously. Using genetic mutation data, we determined that 6 of the 30 genes showed significant differences (adjusted p-value < 0.05) in mutation frequencies between the primary PCa and metastasis PCa samples. The identified 30 genes performed well in distinguishing PCa patients with metastasis from PCa patient without metastasis (area under the receiver operating characteristic curve (AUC) = 0.81). The gene signature also performed well in distinguishing PCa patients with high risk of progression from PCa patients with low risk of progression (AUC = 0.88). Conclusions: We established an integrative framework to identify differentially expressed genes with an aberrant methylation pattern on PP adipose tissue that may represent novel candidate molecular markers for distinguishing between LPC and LAPC.
  • Autores: Fruhbeck Martínez, Gema; Catalán Goñi, Victoria; Ramírez, B.; et al.
    Revista: JOURNAL OF INFLAMMATION RESEARCH
    ISSN: 1178-7031 Vol.15 2022 págs. 1331 - 1345
    Resumen
    Background: Excess adiposity leads to a dysfunctional adipose tissue that contributes to the development of obesity-associated comorbidities such as type 2 diabetes (T2D). Interleukin-1 receptor antagonist (IL-1RA) is a naturally occurring antagonist of the IL-1 receptor with anti-inflammatory properties. The aim of the present study was to compare the circulating concentrations of IL-1RA and its mRNA expression in visceral adipose tissue (VAT) in subjects with normal weight (NW), obesity with normoglycemia (OB-NG), or obesity with impaired glucose tolerance or T2D (OB-IGT&T2D) and to analyze the effect of changes in body fat percentage (BF%) on IL-1RA levels. Methods: Serum concentrations of IL-1RA were measured in 156 volunteers. Expression of IL1RN mRNA in VAT obtained from 36 individuals was determined. In addition, the concentrations of IL-1RA were measured before and after weight gain as well as weight loss following a dietetic program or Roux-en-Y gastric bypass (RYGB). Results: Serum levels of IL-1RA were significantly increased in individuals with obesity, being further increased in the OBIGT&T2D group (NW 440 +/- 316, OB-NG 899 +/- 562, OB-IGT&T2D 1265 +/- 739 pg/mL; P<0.001) and associated with markers of inflammation and fatty liver. IL1RN mRNA expression in VAT was significantly increased in the OB-IGT&T2D group and correlated in the global cohort with the mRNA expression of SPP1, CCL2, CD68, and MMP9. Levels of IL-1RA were not modified after modest changes in BF%, but RYGB-induced weight loss significantly decreased IL-1RA concentrations from 1233 +/- 1009 to 660 +/- 538 pg/ mL (P<0.001). Conclusion: Serum IL-1RA concentrations are increased in patients with obesity being further elevated in obesity-associated IGT and T2D in association with markers of adipose tissue dysfunction. The mRNA expression of IL1RN is markedly increased in VAT of subjects with obesity and T2D in relation with genes involved in macrophage recruitment, inflammation and matrix remodeling. Serum IL-1RA concentrations are reduced when a notable amount of BF% is loss. Measurement of IL-1RA is an excellent biomarker of adipose tissue dysfunction in obesity-associated metabolic alterations.
  • Autores: Fernández González, Secundino (Autor de correspondencia); Ferrán de la Cierva, Sol; Garaycochea Mendoza del Solar, Octavio
    Revista: CLINICAL CASE REPORTS
    ISSN: 2050-0904 Vol.10 N° 3 2022 págs. e05476
    Resumen
    We report the case of a 48-year-old woman, a teacher, with recurrent severe dysphonia and multiple and different lesions at the same time in her vocal folds. The evolution of the lesions and the possible mechanism by which they have been associated in the same patient are commented.
  • Autores: Fruhbeck Martínez, Gema (Autor de correspondencia); Gómez Ambrosi, Javier; Ramírez, B.; et al.
    Revista: FRONTIERS IN IMMUNOLOGY
    ISSN: 1664-3224 Vol.13 2022 págs. 832185
    Resumen
    Interleukin (IL)-36 is a recently described cytokine with well-known functions in the regulation of multiple inflammatory diseases. Since no data exists on how this cytokine regulates adipose tissue (AT) homeostasis, we aimed to explore the function of a specific isoform, IL-36 gamma, an agonist, in human obesity and obesity-associated type 2 diabetes as well as in AT inflammation and fibrosis. Plasma IL-36 gamma was measured in 91 participants in a case-control study and the effect of weight loss was evaluated in 31 patients with severe obesity undergoing bariatric surgery. Gene expression levels of IL36G and its receptor were analyzed in relevant human metabolic tissues. The effect of inflammatory factors and IL-36 gamma was determined in vitro in human adipocytes and macrophages. We found, for the first time, that the increased (P<0.05) circulating levels of IL-36 gamma in patients with obesity decreased (P<0.001) after weight and fat loss achieved by Roux-en-Y gastric bypass and that gene expression levels of IL36G were upregulated in the visceral AT (P<0.05) and in the peripheral blood mononuclear cells (P<0.01) from patients with obesity. We also demonstrated increased (P<0.05) expression levels of Il36g in the epididymal AT from diet-induced obese mice. IL36G was significantly enhanced (P<0.001) by LPS in human adipocytes and monocyte-derived macrophages, while no changes were found after the incubation with anti-inflammatory cytokines. The addition of IL-36 gamma for 24 h strongly induced (P<0.01) its own expression as well as key inflammatory and chemoattractant factors with no changes in genes associated with fibrosis. Furthermore, adipocyte-conditioned media obtained from patients with obesity increased (P<0.01) the release of IL-36 gamma and the expression (P<0.05) of cathepsin G (CTSG) in monocyte-derived macrophages. These findings provide, for the first time, evidence about the properties of IL-36 gamma in the regulation of AT-chronic inflammation, emerging as a link between AT biology and the obesity-associated comorbidities.
  • Autores: Garaycochea Mendoza del Solar, Octavio (Autor de correspondencia); Baptista Jardín, Peter Michael; Calvo Imirizaldu, Marta; et al.
    Revista: EUROPEAN ARCHIVES OF OTO-RHINO-LARYNGOLOGY
    ISSN: 0937-4477 Vol.279 N° 11 2022 págs. 5347 - 5353
    Resumen
    Purpose To describe the anatomic relationship of the lingual nerve with the lateral oropharyngeal structures. Methods An anatomic dissection of the lateral oropharyngeal wall was conducted in eight sides from four fresh-frozen cadaveric heads. Small titanium clips were placed along the lingual nerve and the most anterior and medial border of the medial pterygoid muscle. Radiological reconstructions were employed for optimal visualization; the coronal view was preferred to resemble the surgical position. The distance between the lingual nerve and the medial pterygoid muscle at its upper and lower portion was measured radiologically. The trajectory angle of the lingual nerve with respect to the pterygomandibular raphe was obtained from the intersection between the vector generated between the clips connecting the upper and lower portion of the medial pterygoid muscle with the vector generated from the lingual nerve clips. Results The mean distance from the upper portion of the medial pterygoid muscle and superior lingual nerve clips was 10.16 +/- 2.18 mm (mean +/- standard deviation), and the lower area of the medial pterygoid muscle to the lingual nerve was separated 5.05 +/- 1.49 mm. The trajectory angle of the lingual nerve concerning to the vector that describes the upper portion of the most anterior and medial border of the medial pterygoid muscle with its lower part was 43.73o +/- 11.29. Conclusions The lingual nerve runs lateral to the lateral oropharyngeal wall, from superiorly-inferiorly and laterally-medially, and it is closer to it at its lower third.
  • Autores: Di Ciaula, A.; Bonfrate, L.; Krawczyk, M.; et al.
    Revista: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
    ISSN: 1422-0067 Vol.23 N° 5 2022 págs. 2636
    Resumen
    Nonalcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD) are the most common liver disorders worldwide and the major causes of non-viral liver cirrhosis in the general population. In NAFLD, metabolic abnormalities, obesity, and metabolic syndrome are the driving factors for liver damage with no or minimal alcohol consumption. ALD refers to liver damage caused by excess alcohol intake in individuals drinking more than 5 to 10 daily units for years. Although NAFLD and ALD are nosologically considered two distinct entities, they show a continuum and exert synergistic effects on the progression toward liver cirrhosis. The current view is that low alcohol use might also increase the risk of advanced clinical liver disease in NAFLD, whereas metabolic factors increase the risk of cirrhosis among alcohol risk drinkers. Therefore, special interest is now addressed to individuals with metabolic abnormalities who consume small amounts of alcohol or who binge drink, for the role of light-to-moderate alcohol use in fibrosis progression and clinical severity of the liver disease. Evidence shows that in the presence of NAFLD, there is no liver-safe limit of alcohol intake. We discuss the epidemiological and clinical features of NAFLD/ALD, aspects of alcohol metabolism, and mechanisms of damage concerning steatosis, fibrosis, cumulative effects, and deleterious consequences which include hepatocellular carcinoma.
  • Autores: Gómez-Peralta, F.; Carrasco-Sánchez, F. J.; Pérez, A.; et al.
    Revista: REVISTA CLINICA ESPAÑOLA
    ISSN: 0014-2565 Vol.222 N° 8 2022 págs. 496 - 499
    Resumen
    The population with type 2 DM (DM2) is highly heterogeneous, representing an important challenge for healthcare professionals. The therapeutic choice should be individualized, considering the functional status, frailty, the occurrence of comorbidities, and the preferences of patients and their caregivers. New evidence on the cardiovascular and renal protection of specific therapeutic groups and on the usefulness of new technologies for DM2 management, among other aspects, warrant an update of the consensus document on the DM2 in the elderly that was published in 2018. (C) 2022 The Authors. Published by Elsevier Espana, S.L.U.
  • Autores: León-Jiménez, D. (Autor de correspondencia); Miramontes-González, J. P. (Autor de correspondencia); Márquez-López, L.; et al.
    Revista: DIABETIC MEDICINE
    ISSN: 0742-3071 Vol.39 N° 2 2022 págs. e14679
    Resumen
    Background Diabetic kidney disease is the leading cause of chronic kidney disease (CKD) and end-stage kidney disease (ESKD) worldwide. ESKD has a high prevalence in patients with diabetes mellitus (DM). CKD increases the chances of hypoglycaemia by different mechanisms, causes insulin resistance and a decrease in insulin metabolism. Both the "Kidney Disease: Improving Global Outcomes" (KDIGO) and "American Diabetes Association" (ADA) guidelines recommend the use of insulin as part of treatment, but the type of basal insulin is not specified. Methods We reviewed the literature to determine whether first- and second-generation basal insulins are effective and safe in CKD patients. We reviewed specific pivotal studies conducted by pharmaceutical laboratories, as well as independent studies. Conclusions Basal insulins are safe and effective in patients with CKD and diabetes mellitus but we do not have specific studies. Given that CKD is one of the main complications of type 2 DM, and insulin specific treatment in the final stages, the absence of studies is striking. Real-life data are also important since trials such as pivotal studies do not fully represent actual patients. Treatment should be individualized until we have specific trials in this type of population.
  • Autores: Ripolles-Melchor, J.; Sánchez-Santos, R.; Abad-Motos, A. (Autor de correspondencia); et al.
    Revista: OBESITY SURGERY
    ISSN: 0960-8923 Vol.32 N° 4 2022 págs. 1289 - 1299
    Resumen
    Purpose: The effectiveness of enhanced recovery after surgery (ERAS) pathways in patients undergoing bariatric surgery remains unclear. Our objective was to determine the effect of the ERAS elements on patient outcomes following elective bariatric surgery. Materials and methods: Prospective cohort study in adult patients undergoing elective bariatric surgery. Each participating center selected a single 3-month data collection period between October 2019 and September 2020. We assessed the 24 individual components of the ERAS pathways in all patients. We used a multivariable and multilevel logistic regression model to adjust for baseline risk factors, ERAS elements, and center differences RESULTS: We included 1419 patients. One hundred and fourteen patients (8%) developed postoperative complications. There were no differences in the incidence of overall postoperative complications between the self-designated ERAS and non-ERAS groups (54 (8.7%) vs. 60 (7.6%); OR, 1.14; 95% CI, 0.73-1.79; P = .56), neither for moderate-to-severe complications, readmissions, re-interventions, mortality, or hospital stay (2 [IQR 2-3] vs. 3 [IQR 2-4] days, 0.85; 95% CI, 0.62-1.17; P = .33) Adherence to the ERAS elements in the highest adherence quartile (Q1) was greater than 72.2%, while in the lowest adherence quartile (Q4) it was less than 55%. Patients with the highest adherence rates had shorter hospital stay (2 [IQR 2-3] vs. 3 [IQR 2-4] days, 1.54; 95% CI, 1.09-2.17; P = .015), while there were no differences in the other outcomes CONCLUSIONS: Higher adherence to ERAS Society® recommendations was associated with a shorter hospital stay without an increase in postoperative complications or readmissions.
  • Autores: Donini, L. M. (Autor de correspondencia); Busetto, L.; Bischoff, S. C.; et al.
    Revista: CLINICAL NUTRITION
    ISSN: 0261-5614 Vol.41 N° 4 2022 págs. 990 - 1000
    Resumen
    Introduction: Loss of skeletal muscle mass and function (sarcopenia) is common in individuals with obesity due to metabolic changes associated with a sedentary lifestyle, adipose tissue derangements, comorbidities (acute and chronic diseases), and during the ageing process. Co-existence of excess adiposity and low muscle mass/function is referred to as sarcopenic obesity (SO), a condition increasingly recognized for its clinical and functional features that negatively influence important patient-centred outcomes. Effective prevention and treatment strategies for SO are urgently needed, but efforts are hampered by the lack of an universally established SO Definition and diagnostic criteria. Resulting inconsistencies in the literature also negatively affect the ability to define prevalence as well as clinical relevance of SO for negative health outcomes. Aims and methods: The European Society for Clinical Nutrition and Metabolism (ESPEN) and the European Association for the Study of Obesity (EASO) launched an initiative to reach expert consensus on a Definition and diagnostic criteria for SO. The jointly appointed international expert panel proposes that SO is defined as the co-existence of excess adiposity and low muscle mass/function. The diagnosis of SO should be considered in at-risk individuals who screen positive for a co-occurring elevated body mass index or waist circumference, and markers of low skeletal muscle mass and function (risk factors, clinical symptoms, or validated questionnaires). Diagnostic procedures should initially include assessment of skeletal muscle function, followed by assessment of body composition where presence of excess adiposity and low skeletal muscle mass or related body compartments confirm the diagnosis of SO. Individuals with SO should be further stratified into Stage I in the absence of clinical complications, or Stage II if cases are associated with complications linked to altered body composition or skeletal muscle dysfunction. Conclusions: ESPEN and EASO, as well as the expert international panel, advocate that the proposed SO Definition and diagnostic criteria be implemented into routine clinical practice. The panel also encourages prospective studies in addition to secondary analysis of existing datasets, to study the predictive value, treatment efficacy, and clinical impact of this SO definition.
  • Autores: Mentxaka, A.; Gómez Ambrosi, Javier; Ramírez, B.; et al.
    Revista: NUTRIENTS
    ISSN: 2072-6643 Vol.14 N° 20 2022 págs. 4372
    Resumen
    Netrin (NTN)-1 exhibits pro- and anti-inflammatory roles in different settings, playing important roles in the obesity-associated low-grade chronic inflammation. We aimed to determine the impact of NTN-1 on obesity and obesity-associated type 2 diabetes, as well as its role in visceral adipose tissue (VAT) inflammation. A total of 91 subjects were enrolled in this case-control study. Circulating levels of NTN-1 and its receptor neogenin (NEO)-1 were determined before and after weight loss achieved by caloric restriction and bariatric surgery. mRNA levels of NTN1 and NEO1 were assessed in human VAT, liver, and peripheral blood mononuclear cells. In vitro studies in human visceral adipocytes and human monocytic leukemia cells (THP-1)-derived macrophages were performed to analyze the impact of inflammation-related mediators on the gene expression levels of NTN1 and its receptor NEO1 as well as the effect of NTN-1 on inflammation. Increased (p < 0.001) circulating concentrations of NTN-1 in obesity decreased (p < 0.05) after diet-induced weight loss being also associated with a reduction in glucose (p < 0.01) and insulin levels (p < 0.05). Gene expression levels of NTN1 and NEO1 were upregulated (p < 0.05) in the VAT from patients with obesity with the highest expression in the stromovascular fraction cells compared with mature adipocytes (p < 0.01). NTN1 expression levels were enhanced (p < 0.01) under hypoxia and by inflammatory factors in both adipocytes and macrophages. Adipocyte-conditioned media strongly upregulated (p < 0.001) the mRNA levels of NTN1 in macrophages. The treatment of adipocytes with NTN-1 promoted the upregulation (p < 0.05) of pro-inflammatory and chemotactic molecules as well as its receptor NEO1. Collectively, these findings suggest that NTN-1 regulates VAT chronic inflammation and insulin resistance in obesity.
  • Autores: Gargallo-Fernández, M. A.; Tejera-Pérez, C.; Escalada San Martín, Francisco Javier
    Revista: DIABETES RESEARCH AND CLINICAL PRACTICE
    ISSN: 0168-8227 Vol.193 2022 págs. 110137
    Resumen
    Aim: To determine the characteristics of people with type 1 diabetes mellitus (T1D) who practice sports, the support they receive, and the way in which they manage their disease during sports. Methods: An observational cross-sectional study designed as a web-based survey released through social media was carried out, directed to physically active people with T1D. Results: A total of 342 subjects completed the survey (16 children; 67.5% males). The duration of living with T1D was 18.6 +/- 11.4 years. The mean glycosylated hemoglobin concentration (HbA1c) was 6.7 +/- 0.8%, and the mean time in range (TIR) was 72.9 +/- 15.8%. Only 27.2% started sports activity following the diagnosis of T1D. The most frequently used basal insulin was insulin degludec (38.6%). The usual treatment modification before doing sports consisted of bolus reduction (42.5%) or only the adjustment of nutritional supplements (19.7%). In cases of long-acting insulin users, the basal dose usually remained unchanged during sports. One-quarter of the participants were insulin pump users, and of these, 12.5% always disconnected the pump during physical ac-tivities. Severe hypoglycemia on the day of physical activity was experienced by 5% of the participants in the last 6 months. One-third reported a lack of support from their physician, and 61% had learned to manage glycemic control during sports by themselves. Conclusions: This study highlights the adjustments made by people living with T1D during sports practice, and the lack of support received from healthcare professionals.
  • Autores: Baenas, I.; Etxandi, M.; Munguia, L.; et al.
    Revista: NUTRIENTS
    ISSN: 2072-6643 Vol.14 N° 1 2022 págs. 100
    Resumen
    Background. The COVID-19 lockdown has had a significant impact on mental health. Patients with eating disorders (ED) have been particularly vulnerable. Aims. (1) To explore changes in eating-related symptoms and general psychopathology during lockdown in patients with an ED from various European and Asian countries; and (2) to assess differences related to diagnostic ED subtypes, age, and geography. Methods. The sample comprised 829 participants, diagnosed with an ED according to DSM-5 criteria from specialized ED units in Europe and Asia. Participants were assessed using the COVID-19 Isolation Scale (CIES). Results. Patients with binge eating disorder (BED) experienced the highest impact on weight and ED symptoms in comparison with other ED subtypes during lockdown, whereas individuals with other specified feeding and eating disorders (OFSED) had greater deterioration in general psychological functioning than subjects with other ED subtypes. Finally, Asian and younger individuals appeared to be more resilient. Conclusions. The psychopathological changes in ED patients during the COVID-19 lockdown varied by cultural context and individual variation in age and ED diagnosis. Clinical services may need to target preventive measures and adapt therapeutic approaches for the most vulnerable patients.
  • Autores: Baixauli Fons, Jorge; Álvarez-Cienfuegos Suárez, Francisco Javier (Autor de correspondencia); Martínez Regueira, Fernando; et al.
    Revista: SURGICAL LAPAROSCOPY ENDOSCOPY AND PERCUTANEOUS TECHNIQUES
    ISSN: 1530-4515 Vol.32 N° 1 2022 págs. 28 - 34
    Resumen
    Background: Laparoscopic resection is the treatment of choice for colorectal cancer. Rates of conversion to open surgery range between 7% and 30% and controversy exists as to the effect of this on oncologic outcomes. The objective of this study was to analyze what factors are predictive of conversion and what effect they have on oncologic outcomes. Methods: From a prospective database of patients undergoing laparoscopic surgery between 2000 and 2018 a univariate and multivariate analyses were made of demographic, pathologic, and surgical variables together with complementary treatments comparing purely laparoscopic resection with conversions to open surgery. Overall and disease-free survival were compared using the Kaplan-Meier method. Results: Of a total of 829 patients, 43 (5.18%) converted to open surgery. In the univariate analysis, 12 variables were significantly associated with conversion, of which left-sided resection [odds ratio (OR): 2.908; P=0.02], resection of the rectum (OR: 4.749, P=0.014), and local invasion of the tumor (OR: 6.905, P<0.01) were independently predictive factors in the multiple logistic regression. Female sex was associated with fewer conversions (OR: 0.375, P=0.012). The incidence and pattern of relapses were similar in both groups and there were no significant differences between overall and disease-free survival. Conclusions: Left-sided resections, resections of the rectum and tumor invasion of neighboring structures are associated with higher rates of conversion. Female sex is associated with fewer conversions. Conversion to open surgery does not compromise oncologic outcomes at 5 and 10 years.
  • Autores: Fruhbeck Martínez, Gema (Autor de correspondencia); Becerril Mañas, Sara; Martín Rodríguez, Marina; et al.
    Revista: METABOLISM-CLINICAL AND EXPERIMENTAL
    ISSN: 0026-0495 Vol.128 2022 págs. 155119
    Resumen
    Background: The biological mediators supporting long-term weight loss and changes in dietary choice behaviour after sleeve gastrectomy remain unclear. Guanylin and uroguanylin are gut hormones involved in the regulation of satiety, food preference and adiposity. Thus, we sought to analyze whether the guanylin system is involved in changes in food preference after sleeve gastrectomy in obesity. Methods: Proguanylin (GUCA2A) and prouroguanylin (GUCA2B) were determined in patients with severe obesity (n = 41) as well as in rats with diet-induced obesity (n = 48), monogenic obesity (Zucker fa/fa) (n = 18) or in a food choice paradigm (normal diet vs high-fat diet) (n = 16) submitted to sleeve gastrectomy. Lingual distribution and expression of guanylins (GUCA2A and GUCA2B) and their receptor GUCY2C as well as the fatty acid receptor CD36 were evaluated in the preclinical models. Results: Circulating concentrations of GUCA2A and GUCA2B were increased after sleeve gastrectomy in patients with severe obesity as well as in rats with diet-induced and monogenic (fa/fa) obesity. Interestingly, the lower dietary fat preference observed in obese rats under the food choice paradigm as well as in patients with obesity after sleeve gastrectomy were negatively associated with post-surgical GUCA2B levels. Moreover, sleeve gastrectomy upregulated the low expression of GUCA2A and GUCA2B in taste bud cells of tongues from rats with diet induced and monogenic (fa/fa) obesity in parallel to a downregulation of the lingual lipid sensor CD36. Conclusions: The increased circulating and lingual GUCA2B after sleeve gastrectomy suggest an association between the uroguanylin-GUCY2C endocrine axis and food preference through the regulation of gustatory responses. (c) 2022 Elsevier Inc. All rights reserved.
  • Autores: Yárnoz-Esquiroz, P.; Olazarán, L.; Aguas-Ayesa, M.; et al.
    Revista: EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
    ISSN: 0014-2972 Vol.52 N° 7 2022 págs. e13811
    Resumen
    Academic medicine fosters research that moves from discovery to translation, at the same time as promoting education of the next generation of professionals. In the field of obesity, the supposed integration of knowledge, discovery and translation research to clinical care is being particularly hampered. The classification of obesity based on the body mass index does not account for several subtypes of obesity. The lack of a universally shared definition of "obesities" makes it impossible to establish the real burden of the different obesity phenotypes. The individual's genotype, adipotype, enterotype and microbiota interplays with macronutrient intake, appetite, metabolism and thermogenesis. Further investigations based on the concept of differently diagnosed "obesities" are required.
  • Autores: Hurtado-Pardo, L.; Breeze, C. E.; Álvarez-Cienfuegos Suárez, Francisco Javier (Autor de correspondencia); et al.
    Revista: REVISTA ESPAÑOLA DE ENFERMEDADES DIGESTIVAS
    ISSN: 1130-0108 Vol.114 N° 6 2022 págs. 317 - 322
    Resumen
    Background and aim: fifty to 70 percent of pancreatic neuro-endocrine tumors are diagnosed incidentally. The objective of this study was to compare the phenotype and oncologi-cal outcomes of incidental versus symptomatic pancreatic neuroendocrine tumors. Methods: a retrospective study was performed, identifying all incidental and symptomatic tumors resected between 2000 and 2019. Baseline characteristics, symptoms, oper-ative variables and pathological stage were all recorded. Patterns of recurrence and overall and disease-free survival were analyzed in both groups. Results: fifty-one incidental and 45 symptomatic pancreat-ic tumor resections were performed. Symptomatic tumors were more frequent in females (29 vs 17; p = 0.005) and younger patients (median years; 50 vs 58; p = 0.012) and were detected at a more advanced stage (p = 0.027). There were no differences in location and most resections (n = 49; 51 %) were performed laparoscopically. There were no operative mortalities and 17 (17.7 %) severe com-plications (>_ IIIb on the Clavien-Dindo classification) were recorded with no differences between the two groups. With a median follow-up of 64.4 months (range 13.5-90), overall survival at five and ten years was 89.7 % and 72.8 % for the non-incidental tumors and 80.9 % and 54.6 % for the incidental tumors (p = ns), respectively. Disease-free survival in both groups (excluding M1a) was 71.2 % and 47.5 %, and 93.7 % and 78.1 %, respectively (p = ns). Conclusions: symptomatic tumors are more frequent in females and present at more advanced pathological stag-es. There were no significant differences in overall and disease-free survival between the two groups. Resection of incidental tumors >_ 1.5-2 cm seems advisable, although each case should be assessed on an individual basis.
  • Autores: Gargallo-Fernández, M. (Autor de correspondencia); Escalada San Martín, Francisco Javier; Chico-Ballesteros, A.; et al.
    Revista: ENDOCRINOLOGIA DIABETES Y NUTRICION
    ISSN: 2530-0180 Vol.69 N° 9 2022 págs. 732 - 743
    Resumen
    Objective: To guide professionals involved in the care of people with diabetes mellitus who practice sport.Participants: Members of the Diabetes Mellitus Working Group of the Spanish Society of Endo-crinology and Nutrition.Methods: A group of experts in each area covered by the statement carried out a bibliograp-hic review of the available evidence for each topic, based on which recommendations were subsequently agreed upon within the Diabetes Mellitus Working Group.Conclusions: The statement provides practical recommendations for the management of dia-betes mellitus during sports practice.(c) 2021 SEEN y SED. Published by Elsevier Espana, S.L.U. All rights reserved.
  • Autores: Becerril Mañas, Sara (Autor de correspondencia); Tuero Ojanguren, Carlota; Álvarez-Cienfuegos Suárez, Francisco Javier; et al.
    Revista: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
    ISSN: 1422-0067 Vol.23 N° 19 2022 págs. 11641
    Resumen
    Bariatric surgery has been recognized as the safest and most effective procedure for controlling type 2 diabetes (T2D) and obesity in carefully selected patients. The aim of the present study was to compare the effects of Sleeve Gastrectomy (SG) and Single Anastomosis Duodenoileal Bypass with SG (SADI-S) on the metabolic profile of diet-induced obese rats. A total of 35 four-week-old male Wistar rats were submitted to surgical interventions (sham operation, SG and SADI-S) after 4 months of being fed a high-fat diet. Body weight, metabolic profile and the expression of molecules involved in the control of subcutaneous white (SCWAT), brown (BAT) and beige (BeAT) adipose tissue function were analyzed. SADI-S surgery was associated with significantly decreased amounts of total fat pads (p < 0.001) as well as better control of lipid and glucose metabolism compared to the SG counterparts. An improved expression of molecules involved in fat browning in SCWAT and in the control of BAT and BeAT differentiation and function was observed following SADI-S. Together, our findings provide evidence that the enhanced metabolic improvement and their continued durability after SADI-S compared to SG rely, at least in part, on the improvement of the BeAT phenotype and function.
  • Autores: Unamuno Iñurritegui, Xabier; Gómez Ambrosi, Javier; Becerril Mañas, Sara; et al.
    Revista: ACTA BIOMATERIALIA
    ISSN: 1742-7061 Vol.141 2022 págs. 264 - 279
    Resumen
    Biomechanical properties of adipose tissue (AT) are closely involved in the development of obesity associated comorbidities. Bariatric surgery (BS) constitutes the most effective option for a sustained weight loss in addition to improving obesity-associated metabolic diseases including type 2 diabetes (T2D). We aimed to determine the impact of weight loss achieved by BS and caloric restriction (CR) on the biomechanical properties of AT. BS but not CR changed the biomechanical properties of epididymal white AT (EWAT) from a diet-induced obesity rat model, which were associated with metabolic improvements. We found decreased gene expression levels of collagens and Lox together with increased elastin and Mmps mRNA levels in EWAT after BS, which were also associated with the biomechanical properties. Moreover, an increased blood vessel density was observed in EWAT after surgery, confirmed by an up regulation of Acta2 and Antxr1 gene expression levels, which was also correlated with the biomechanical properties. Visceral AT from patients with obesity showed increased stiffness after tensile tests compared to the EWAT from the animal model. This study uncovers new insights into EWAT adaptation after BS with decreased collagen crosslink and synthesis as well as an increased degradation together with enhanced blood vessel density providing, simultaneously, higher stiffness and more ductility. Statement of Significance Biomechanical properties of the adipose tissue (AT) are closely involved in the development of obesity associated comorbidities. In this study, we show for the first time that biomechanical properties of AT determined by E , UTS and strain at UTS are decreased in obesity, being increased after bariatric surgery by the promotion of ECM remodelling and neovascularization. Moreover, these changes in biomechanical properties are associated with improvements in metabolic homeostasis. Consistently, a better characterization of the plasticity and biomechanical properties of the AT after bariatric surgery opens up a new field for the development of innovative strategies for the reduction of fibrosis and inflammation in AT as well as to better understand obesity and its associated comorbidities.
  • Autores: Zugasti-Murillo, A.; Tejera-Pérez, C. (Autor de correspondencia); Rubio-Herrera, M. A.; et al.
    Revista: ENDOCRINOLOGIA DIABETES Y NUTRICION
    ISSN: 2530-0180 Vol.69 N° 3 2022 págs. 219 - 226
    Resumen
    Introducción La enfermedad COVID-19 se ha convertido en una prioridad para nuestro sistema sanitario. Los MIR de Endocrinología y Nutrición (MIR-EyN) se han integrado en los equipos COVID-19. Se ha diseñado este estudio con el objetivo de analizar el impacto a nivel formativo, laboral y en la salud de los MIR-EyN. Material y métodos Estudio observacional transversal tipo encuesta vía web, dirigida a los MIR-EyN socios de la SEEN, realizado en noviembre de 2020. Se han analizado: variables demográficas, tamaño del hospital de formación en número de camas, alteración de las rotaciones, integración en equipos COVID-19, participación en teleconsulta, actividad científica e impacto sobre la salud física y emocional. Resultados Se han obtenido 87 respuestas (27% de los MIR-EyN); 67,8% mujeres, edad media 28,1 ± 1,8 años, 60% MIR-EyN 4.o año. El 84% ha participado en equipos COVID-19 y el 93% en las consultas telemáticas de su servicio. La mayoría ha visto interrumpidas sus rotaciones. El 97,7% ha participado en reuniones científicas o congresos virtuales y un tercio de ellos ha colaborado en trabajos científicos sobre la COVID-19 en relación con la Endocrinología y Nutrición. La pandemia ha afectado a su estado de ánimo mucho o bastante (75,8%) y opinan que ha impactado de forma negativa a su formación (73,8%). Conclusiones La pandemia por SARS-CoV-2 ha comprometido la formación, la actividad laboral y la salud de los MIR-EyN. Se han integrado tanto en equipos COVID-19 como en la actividad reestructurada de sus servicios. Sin embargo, han conseguido mantener la formación en formato virtual y participado en trabajos científicos.
  • Autores: Perdomo Zelaya, Carolina María (Autor de correspondencia); Ezponda Casajús, Ana; Núñez Córdoba, Jorge María; et al.
    Revista: SCIENTIFIC REPORTS
    ISSN: 2045-2322 Vol.12 N° 1 2022 págs. 6564
    Resumen
    Non-alcoholic fatty liver disease (NAFLD) is associated with cardiovascular disease morbimortality. However, it is not clear if NAFLD staging may help identify early or subclinical markers of cardiovascular disease. We aimed to evaluate the association of liver stiffness and serum markers of liver fibrosis with epicardial adipose tissue (EAT) and coronary artery calcium (CAC) in an observational cross-sectional study of 49 NAFLD patients that were seen at Clínica Universidad de Navarra (Spain) between 2009 and 2019. Liver elastography and non-invasive fibrosis markers were used to non-invasively measure fibrosis. EAT and CAC, measured through visual assessment, were determined by computed tomography. Liver stiffness showed a direct association with EAT (r = 0.283, p-value = 0.049) and CAC (r = 0.337, p-value = 0.018). NAFLD fibrosis score was associated with EAT (r = 0.329, p-value = 0.021) and CAC (r = 0.387, p-value = 0.006). The association of liver stiffness with CAC remained significant after adjusting for metabolic syndrome features (including carbohydrate intolerance/diabetes, hypertension, dyslipidaemia, visceral adipose tissue, and obesity). The evaluation of NAFLD severity through liver elastography or non-invasive liver fibrosis biomarkers may contribute to guide risk factor modification to reduce cardiovascular risk in asymptomatic patients. Inversely, subclinical cardiovascular disease assessment, through Visual Scale for CAC scoring, may be a simple and effective measure for patients with potential liver fibrosis, independently of the existence of other cardiovascular risk factors.
  • Autores: Yarnoz-Esquiroz, P. (Autor de correspondencia); Chopitea Ortega, Ana; Olazarán, L.; et al.
    Revista: NUTRIENTS
    ISSN: 2072-6643 Vol.14 N° 13 2022 págs. 2754
    Resumen
    Many studies have demonstrated that malnutrition has a negative impact on quality of life and mortality in patients with cancer. During the SARS-CoV-2 lockdown, dietary intake changes were detected in the Spanish population, reflecting an increase in the consumption of fruit, bread, flours, and eggs. The present study analyzed the nutritional status of 728 patients with cancer admitted once the SARS-CoV-2 lockdown finished, comparing it with the previous year as well as with mortality rates. The Malnutrition Universal Screening Tool (MUST) was applied in the first 24 h after admission. Age, gender, days of stay, circulating concentrations of albumin, cholesterol, C-reactive protein (CRP), lymphocytes, prealbumin, and mortality data were analyzed. Patients with cancer admitted between June and December of 2020 exhibited no statistical differences in BMI, age, or gender as compared to patients admitted in 2019. Statistically significant differences in nutritional status (p < 0.05), albumin (p < 0.001), and CRP (p = 0.005) levels regarding lockdown were observed in relation with a small non-significant reduction in mortality. In conclusion, following the SARS-CoV-2 lockdown, an improved nutritional status in cancer patients at admission was observed with a decrease in the percentage of weight loss and CRP levels together with an increase in albumin levels compared to oncological patients admitted the previous year.
  • Autores: Martínez-Arellano, A.; Campo Ezquibela, Aránzazu; Del Río, B.; et al.
    Revista: JOURNAL OF SPEECH LANGUAGE AND HEARING RESEARCH
    ISSN: 1092-4388 Vol.65 N° 10 2022 págs. 3789 - 3797
    Resumen
    Purpose: The aims of this study were to analyze and characterize the irrintzi (a folkloric shout emitted in a single breath used by the Basque people) acoustically and to describe the mechanism by which it is emitted. Method: Thirty-six sound samples of 12 female volunteers were analyzed. Acoustic analysis included primarily fundamental frequency (fo), spectral analysis in the time domain with a narrowband filter, and the use of linear predictive coding (LPC). Laryngeal and pharyngeal movements while emitting an irrintzi were studied by fiberoptic nasal endoscopy. Postural and mandible movements were observed and video recorded. Movements of the larynx and the vocal tract were also studied by lateral pharyngo-laryngeal radioscopy. Results: The central part of an irrintzi spectrogram contains a peculiar, repeated M-shaped motif unseen in the spectrogram of any other human vocal emission, and intensity was over 90 dB SPL in all cases. fo was very high (1487 Hz) especially at the end of the irrintzi. Fiberoptic nasal endoscopy consistently revealed considerable elevation of the glottis, with the larynx swinging forward and retraction of the ventricular bands. Lateral radioscopy showed a very high larynx and a high tongue dorsum. Conclusions: The irrintzi is a sound emitted in a single breath and characterized by its shrillness and loudness, qualities that make it audible in noisy environments and over large distances and the vocal technique observed when it is produced can be explained by the Estill voice model (Steinhauer et al., 2017). The use of this technique may help in the treatment of voice disorders and improve efficiency in singers, teachers, actors, and people who use their voice at high volume or at high frequency.
  • Autores: Catalán Goñi, Victoria (Autor de correspondencia); Domench, P.; Gómez Ambrosi, Javier; et al.
    Revista: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
    ISSN: 1422-0067 Vol.23 N° 16 2022 págs. 9222
    Resumen
    Dysfunctional adipose tissue (AT) in the context of obesity leads to chronic inflammation together with an altered extracellular matrix (ECM) remodelling, favouring cancer development and progression. Recently, the influence of dermatopontin (DPT) in AT remodelling and inflammation has been proposed. We aimed to evaluate the role of DPT in the development of obesity-associated colon cancer (CC). Samples obtained from 73 subjects [26 lean (LN) and 47 with obesity (OB)] were used in a case-control study. Enrolled subjects were further subclassified according to the established diagnostic protocol for CC (42 without CC and 31 with CC). In vitro studies in the adenocarcinoma HT-29 cell line were performed to analyse the impact of pro- and anti-inflammatory mediators on the transcript levels of DPT as well as the effect of DPT on ECM remodelling and inflammation. Although obesity increased (p < 0.05) the circulating levels of DPT, its concentrations were significantly decreased (p < 0.05) in patients with CC. Gene expression levels of DPT in the colon from patients with CC were downregulated and, oppositely, a tendency towards increased mRNA levels in visceral AT was found. We further showed that DPT expression levels in HT-29 cells were enhanced (p < 0.05) by inflammatory factors (LPS, TNF-alpha and TGF-beta), whereas the anti-inflammatory IL-4 decreased (p < 0.05) its expression levels. We also demonstrated that DPT upregulated (p < 0.05) the mRNA of key molecules involved in ECM remodelling (COL1A1, COL5A3, TNC and VEGFA) whereas decorin (DCN) expression was downregulated (p < 0.05) in HT-29 cells. Finally, we revealed that the adipocyte-conditioned medium obtained from volunteers with OB enhanced (p < 0.01) the expression of DPT in HT-29 and Caco-2 cells. The decreased circulating and expression levels of DPT in the colon together with the tendency towards increased levels in visceral AT in patients with CC and its influence on the expression of ECM proteins suggest a possible role of DPT in the OB-associated CC.
  • Autores: Gómez Ambrosi, Javier
    Revista: EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
    ISSN: 0014-2972 Vol.52 N° Supl. 1 2022
  • Autores: Fruhbeck Martínez, Gema; Catalán Goñi, Victoria; Valentí Azcarate, Víctor; et al.
    Revista: EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
    ISSN: 0014-2972 Vol.52 N° Supl. 1 2022
  • Autores: Bonfrate, L.; Wang, D. Q. H.; Fruhbeck Martínez, Gema; et al.
    Revista: EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
    ISSN: 0014-2972 Vol.52 N° Supl. 1 2022
  • Autores: Fruhbeck Martínez, Gema; Gómez Ambrosi, Javier; Ramírez, B.; et al.
    Revista: EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
    ISSN: 0014-2972 Vol.52 N° Supl. 1 2022
  • Autores: Fruhbeck Martínez, Gema; Catalán Goñi, Victoria; Ramírez, B.; et al.
    Revista: EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
    ISSN: 0014-2972 Vol.52 N° Supl. 1 2022
  • Autores: Becerril Mañas, Sara; Rodríguez Murueta-Goyena, Amaia; Catalán Goñi, Victoria; et al.
    Revista: EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
    ISSN: 0014-2972 Vol.52 N° Supl. 1 2022
  • Autores: Landecho Acha, Manuel Fortún (Autor de correspondencia); Marin Oto, Marta; Recalde Zamacona, Borja; et al.
    Revista: EUROPEAN JOURNAL OF INTERNAL MEDICINE
    ISSN: 0953-6205 Vol.91 2021 págs. 3 - 9
    Resumen
    Severe Acute Respiratory Syndrome Coronavirus 2 (SARS CoV2) disease (COVID-19) is a novel threat that hampers life expectancy especially in obese individuals. Though this association is clinically relevant, the underlying mechanisms are not fully elucidated. SARS CoV2 enters host cells via the Angiotensin Converting Enzyme 2 receptor, that is also expressed in adipose tissue. Moreover, adipose tissue is also a source of many proinflammatory mediators and adipokines that might enhance the characteristic COVID-19 cytokine storm due to a chronic low-grade inflammatory preconditioning. Further obesity-dependent thoracic mechanical constraints may also incise negatively into the prognosis of obese subjects with COVID-19. This review summarizes the current body of knowledge on the obesity-dependent circumstances triggering an increased risk for COVID-19 severity, and their clinical relevance.
  • Autores: Tuero, C. (Autor de correspondencia); Docio, G.; Valentí Azcarate, Víctor; et al.
    Revista: WORLD JOURNAL OF LAPAROSCOPIC SURGERY
    ISSN: 0974-5092 Vol.14 N° 2 2021 págs. 141 - 143
    Resumen
    Aim and objective: The aim and objective of this article was to focus on long-term complications after bariatric surgery, which are usually managed by general surgeons in the emergency department. Background: Roux-en-Y gastric bypass (RYGBP) is one of the most commonly performed bariatric techniques in the world. Gastric remnant complications after this procedure are infrequent and poorly known. Furthermore, the diagnosis of this pathology may be challenging. Case description: We present the case of a 54-year-old woman with intense epigastric pain and history of uncomplicated laparoscopic RYGBP 18 years ago. After clinical, laboratory, and radiological examinations, the patient was diagnosed with a gastric remnant perforation. Laparoscopic surgery was performed, and the perforation was successfully repaired with primary suture and omental patch. Conclusion: Gastric remnant perforation after bariatric surgery is not frequent and usually appears several years after the procedure. This type of pathology is presented without specific clinical manifestations and with few analytical alterations. Complementary radiological studies, such as computed tomography (CT) scan, should be performed. However, pneumoperitoneum and extravasation of oral contrast are usually absent. Depending on the size of the defect, primary suture or gastric remnant resection may be performed. Nevertheless, surgical treatment should not be delayed. Clinical significance: Long-term complications after bariatric surgery are in many circumstances managed by general practitioner surgeons. The low incidence and scarce manifestations make the diagnosis of this pathology challenging. Furthermore, bariatric surgery is progressively increasing its presence all over the world. Complications after this procedure must be known and kept in mind because an early diagnosis is crucial to give a proper treatment and reduce morbidity and mortality.
  • Autores: Escalada San Martín, Francisco Javier
    Revista: ADVANCES IN LABORATORY MEDICINE / AVANCES EN MEDICINA DE LABORATORIO
    ISSN: 2628-491X Vol.2 N° 3 2021 págs. 309 - 312
  • Autores: Catalán Goñi, Victoria; Rodríguez Murueta-Goyena, Amaia; Becerril Mañas, Sara; et al.
    Revista: EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
    ISSN: 0014-2972 Vol.51 N° 9 2021 págs. e13586
  • Autores: Fondevila, M. F.; Mercado-Gómez, M.; Rodríguez Murueta-Goyena, Amaia; et al.
    Revista: JOURNAL OF HEPATOLOGY (ONLINE)
    ISSN: 0168-8278 Vol.74 N° 2 2021 págs. 469 - 471
  • Autores: Álvarez-Cienfuegos Suárez, Francisco Javier (Autor de correspondencia); Valentí Azcarate, Víctor; Rotellar Sastre, Fernando
    Revista: REVISTA ESPAÑOLA DE ENFERMEDADES DIGESTIVAS
    ISSN: 1130-0108 Vol.113 N° 7 2021 págs. 554 - 554
  • Autores: Álvarez-Cienfuegos Suárez, Francisco Javier (Autor de correspondencia); Valentí Azcarate, Víctor; Rotellar Sastre, Fernando
    Revista: JAMA SURGERY
    ISSN: 2168-6254 Vol.156 N° 12 2021 págs. 1183 - 1183
  • Autores: Reyes-García, R. (Autor de correspondencia); Mezquita-Raya, P.; Moreno-Pérez, O.; et al.
    Revista: ENDOCRINOLOGIA DIABETES Y NUTRICION
    ISSN: 2530-0180 Vol.68 N° 4 2021 págs. 270 - 276
    Resumen
    Objective: To provide practical recommendations for the evaluation and management of hypo-glycemia in patients with diabetes mellitus. Participants: Members of the Diabetes Mellitus Working Group of the Spanish Society of Endo-crinology and Nutrition (SEEN). Methods: The recommendations were made based on the Grading of Recommendations, Assess-ment, Development and Evaluation (GRADE) system to establish both the strength of the recommendations and the level of evidence. A systematic search was made in MEDLINE (Pub -Med) for the available evidence on each subject, and articles written in English and Spanish with an inclusion date up to 28 February 2020 were reviewed. This executive summary takes account of the evidence incorporated since 2013. Conclusions: The document establishes practical evidence-based recommendations regarding the evaluation and management of hypoglycemia in patients with diabetes mellitus.
  • Autores: Currás Freixes, María (Autor de correspondencia); Salvador Rodríguez, Javier
    Revista: REVISTA CLINICA ESPAÑOLA
    ISSN: 0014-2565 Vol.221 N° 1 2021 págs. 30 - 32
  • Autores: Escalada San Martín, Francisco Javier
    Revista: ADVANCES IN LABORATORY MEDICINE / AVANCES EN MEDICINA DE LABORATORIO
    ISSN: 2628-491X Vol.2 N° 3 2021 págs. 305 - 308
  • Autores: Breton, I. (Autor de correspondencia); de Hollanda, A.; Vilarrasa, N.; et al.
    Revista: ENDOCRINOLOGIA DIABETES Y NUTRICION
    ISSN: 2530-0180 Vol.68 N° 8 2021 págs. 573 - 576
  • Autores: Becerril Mañas, Sara; Fruhbeck Martínez, Gema (Autor de correspondencia)
    Revista: LANCET
    ISSN: 0140-6736 Vol.397 N° 10286 2021 págs. 1687 - 1689
  • Autores: Fruhbeck Martínez, Gema; Catalán Goñi, Victoria; Valentí Azcarate, Víctor; et al.
    Revista: CELLULAR AND MOLECULAR IMMUNOLOGY
    ISSN: 1672-7681 Vol.18 N° 10 2021 págs. 2457 - 2459
  • Autores: Dicker, D.; Golan, R. (Autor de correspondencia); Baker, J. L.; et al.
    Revista: OBESITY FACTS
    ISSN: 1662-4025 Vol.14 N° 3 2021 págs. 334 - 335
  • Autores: Garaycochea Mendoza del Solar, Octavio (Autor de correspondencia); Alcalde Navarrete, Juan Manuel; Fernández González, Secundino
    Revista: JOURNAL OF VOICE
    ISSN: 0892-1997 Vol.35 N° 6 2021 págs. 930
  • Autores: Escalada San Martín, Francisco Javier (Autor de correspondencia); Pérez, A.
    Revista: ENDOCRINOLOGIA DIABETES Y NUTRICION
    ISSN: 2530-0180 Vol.68 N° 2 2021 págs. 79 - 81
  • Autores: Landecho Acha, Manuel Fortún; Fruhbeck Martínez, Gema (Autor de correspondencia)
    Revista: OBESITY
    ISSN: 1930-7381 Vol.29 N° 1 2021 págs. 19
    Resumen
    As of October 2020, the Severe Acute Respiratory Syndrome coronavirus 2 (SARS¿CoV¿2), responsible for Coronavirus Disease 2019 (COVID¿19), has infected over 33million individuals and killed over one million people worldwide. (https://coronavirus.jhu.edu/map.html accessed October 1 2020) Obesity and its complications are linked to severe forms of COVID¿19, favouring an increased hospitalization and mortality rate. Despite being the gold¿standard for the treatment of selected individuals with severe obesity, there is scarce information on whether or not bariatric surgery modifies the prognosis of people living with obesity in the current COVID¿19 pandemic. Bel Lassen and colleagues have carried out the first study with a high number of patients in their sample, bringing light into this area of uncertainty. The authors provide evidence of the importance of diabetes itself as a risk factor for severe COVID¿19.
  • Autores: Salvador Rodríguez, Javier (Autor de correspondencia); Puig-Domingo, M.
    Revista: ENDOCRINOLOGIA DIABETES Y NUTRICION
    ISSN: 2530-0180 Vol.68 N° 7 2021 págs. 447 - 449
  • Autores: Zapata Cardenas, Juana Karina; Catalán Goñi, Victoria; Rodríguez Murueta-Goyena, Amaia; et al.
    Revista: NUTRIENTS
    ISSN: 2072-6643 Vol.13 N° 4 2021 págs. 1216
    Resumen
    In children and adolescents, obesity does not seem to depend on a reduction of resting energy expenditure (REE). Moreover, in this young population, the interactions between either age and obesity or between age and gender, or the role of leptin on REE are not clearly understood. To compare the levels of REE in children and adolescents we studied 181 Caucasian individuals (62% girls) classified on the basis of age- and sex-specific body mass index (BMI) percentile as healthy weight (n = 50), with overweight (n = 34), or with obesity (n = 97) and in different age groups: 8-10 (n = 38), 11-13 (n = 50), and 14-17 years (n = 93). REE was measured by indirect calorimetry and body composition by air displacement plethysmography. Statistically significant differences in REE/fat-free mass (FFM) regarding obesity or gender were not observed. Absolute REE increases with age (p < 0.001), but REE/FFM decreases (p < 0.001) and there is an interaction between gender and age (p < 0.001) on absolute REE showing that the age-related increase is more marked in boys than in girls, in line with a higher FFM. Interestingly, the effect of obesity on absolute REE is not observed in the 8-10 year-old group, in which serum leptin concentrations correlate with the REE/FFM (r = 0.48; p = 0.011). In conclusion, REE/FFM is not affected by obesity or gender, while the effect of age on absolute REE is gender-dependent and leptin may influence the REE/FFM in 8-10 year-olds.
  • Autores: Martín Rodríguez, Marina; Rodríguez Murueta-Goyena, Amaia; Gómez Ambrosi, Javier; et al.
    Revista: NUTRIENTS
    ISSN: 2072-6643 Vol.13 N° 7 2021 págs. 2128
    Resumen
    Energy restriction is a first therapy in the treatment of obesity, but the underlying biological mechanisms have not been completely clarified. We analyzed the effects of restriction of high-fat diet (HFD) on weight loss, circulating gut hormone levels and expression of hypothalamic neuropeptides. Ten-week-old male Wistar rats (n = 40) were randomly distributed into four groups: two fed ad libitum a normal diet (ND) (N group) or a HFD (H group) and two subjected to a 25% caloric restriction of ND (NR group) or HFD (HR group) for 9 weeks. A 25% restriction of HFD over 9 weeks leads to a 36% weight loss with regard to the group fed HFD ad libitum accompanied by normal values in adiposity index and food efficiency ratio (FER). This restriction also carried the normalization of NPY, AgRP and POMC hypothalamic mRNA expression, without changes in CART. Caloric restriction did not succeed in improving glucose homeostasis but reduced HFD-induced hyperinsulinemia. In conclusion, 25% restriction of HFD reduced adiposity and improved metabolism in experimental obesity, without changes in glycemia. Restriction of the HFD triggered the normalization of hypothalamic NPY, AgRP and POMC expression, as well as ghrelin and leptin levels.
  • Autores: Llavero Valero, María; Escalada San Martín, Francisco Javier; Martínez González, Miguel Ángel; et al.
    Revista: CLINICAL NUTRITION
    ISSN: 0261-5614 Vol.40 N° 5 2021 págs. 2817 - 2824
    Resumen
    Background & aim: The association between ultra-processed foods (UPF) consumption and the risk of type 2 diabetes (T2D) has not been much explored. We aimed to evaluate the association between consumption of UPF and the incidence of T2D. Methods: We assessed 20,060 participants (61.5% women) from the SUN project (Seguimiento Universidad de Navarra) followed-up every two years (median follow-up 12 years). Food and drink consumption were evaluated through a validated 136-item food frequency questionnaire and grouped according to their degree of processing by the NOVA classification. Participants were categorized into tertiles of UPF consumption adjusted for total energy intake. We fitted Cox proportional hazard models with repeated dietary measurements at baseline and updating information on food consumption after 10 years of follow-up to minimise the potential effect of diet variation. Results: During 215,149 person-years of follow-up, 175 new-onset T2D cases were confirmed. Participants in the highest baseline tertile (high consumption) of UPF consumption had a higher risk of T2D as compared to those in the lowest tertile (multivariable adjusted hazard ratio [HR] 1.53, 95% confidence interval [CI]: 1.06 to 2.22) with a significant dose-response relationship (p for linear trend 1/4 0.024). The multivariable adjusted HR using repeated measurements of UPF intake was 1.65 (95% CI 1.14-2.38) when comparing extreme tertiles. Conclusions: In a highly-educated Mediterranean cohort with a low absolute risk, a higher intake of UPF was independently associated with a higher risk for T2D. These results provide more evidence to encourage the limitation of UPF consumption to reduce the population burden of T2D. (c) 2021 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.
  • Autores: Granero Peiro, Lucia; Álvarez-Cienfuegos Suárez, Francisco Javier (Autor de correspondencia); Baixauli Fons, Jorge; et al.
    Revista: SURGICAL LAPAROSCOPY ENDOSCOPY AND PERCUTANEOUS TECHNIQUES
    ISSN: 1530-4515 Vol.31 N° 5 2021 págs. 558 - 564
    Resumen
    Background: Laparoscopic resection is the ideal treatment of colon cancer. The aim of the study was to analyze the predictive factors for postoperative complications and their impact on oncologic outcomes in laparoscopic resections in colon cancer. Materials and Methods: In all patients undergoing elective laparoscopic surgery the number and degree of severity of postoperative complications were recorded and classified according to Clavien-Dindo. A univariate analysis was made of the demographic, surgical, and oncologic variables of patients with and without complications. The statistically significant variables were then entered into a multivariate model. In both groups overall and disease-free survival were analyzed using Kaplan-Meier estimates. Results: Of 524 patients, 138 (26.3%) experienced some type of complication, 110 less severe (79.7%) and 28 (20.4%) severe. Twenty-nine conversions to open surgery occurred (5.5%) and hospital mortality was 0.2%. In the multivariate analysis, use of corticosteroids [odds ratio (OR): 3.619], oral anticoagulants (OR: 3.49), blood transfusions (OR: 4.30), and conversion to open surgery (OR: 3.93) were significantly associated with the development of complications. However, sigmoid resections were associated with fewer complications (OR: 0.45). Overall 5-year and 10-year survival in both groups, was 83.3%, 74.1%, 76.0%, and 67.1%, respectively (P = 0.18). Disease-free survival at 5 and 10 years, excluding stage IV tumors, was 88.6% and 90.4%, respectively (P = 0.881). Conclusions: The use of corticosteroids, oral anticoagulants, blood transfusions, and conversion to open surgery are all independent predictive factors of postoperative complications. Sigmoid resections are associated with fewer complications. In laparoscopic resections of the colon, complications do not negatively affect long-term oncologic outcomes.
  • Autores: Alfadda, A. A. (Autor de correspondencia); Caterson, I. D.; Coutinho, W.; et al.
    Revista: EUROPEAN JOURNAL OF INTERNAL MEDICINE
    ISSN: 0953-6205 Vol.91 2021 págs. 17 - 25
    Resumen
    Background: The care of people with obesity is often suboptimal due to both physician and patient perceptions about obesity itself and clinical barriers. Using data from the ACTION-IO study, we aimed to identify factors that might improve the quality of obesity care through adoption of the 3D approach (Discussion, Diagnosis and Direction [follow-up]) by healthcare professionals (HCPs). Methods: An online survey was completed by HCPs in 11 countries. Exploratory beta regression analyses identified independent variables associated with each component of the 3D approach. Results: Data from 2,331 HCPs were included in the statistical models. HCPs were significantly more likely to initiate weight discussions and inform patients of obesity diagnoses, respectively, if (odds ratio [95% confidence interval]): they recorded an obesity diagnosis in their patient's medical notes (1.59, [1.43-1.76] and 2.16 [1.94-2.40], respectively); and they were comfortable discussing weight with their patients (1.53 [1.39-1.69] and 1.15 [1.04-1.27]). HCPs who reported feeling motivated to help their patients lose weight were also more likely to initiate discussions (1.36 [1.21-1.53]) and schedule follow-up appointments (1.21 [1.06-1.38]). By contrast, HCPs who lacked advanced formal training in obesity management were less likely to inform patients of obesity diagnoses (0.83 [0.74-0.92]) or schedule follow-up appointments (0.69 [0.62-0.78]). Conclusion: Specific actions that could improve obesity care through the 3D approach include: encouraging HCPs to record an obesity diagnosis; providing tools to help HCPs feel more comfortable initiating weight discussions; and provision of training in obesity management. Clinical trial registration: NCT03584191.
  • Autores: Latorre, J.; Lluch, A.; Ortega, F. J.; et al.
    Revista: PHARMACOLOGICAL RESEARCH
    ISSN: 1043-6618 Vol.166 2021 págs. 105486
    Resumen
    Chronic systemic low-level inflammation in metabolic disease is known to affect adipose tissue biology. Lysozyme (LYZ) is a major innate immune protein but its role in adipose tissue has not been investigated. Here, we aimed to investigate LYZ in human and rodents fat depots, and its possible role in obesity-associated adipose tissue dysfunction. LYZ mRNA and protein were identified to be highly expressed in adipose tissue from subjects with obesity and linked to systemic chronic-low grade inflammation, adipose tissue inflammation and metabolic disturbances, including hyperglycemia, dyslipidemia and decreased markers of adipose tissue adipogenesis. These findings were confirmed in experimental models after a high-fat diet in mice and rats and also in ob/ob mice. Importantly, specific inguinal and perigonadal white adipose tissue lysozyme (Lyz2) gene knockdown in high-fat diet-fed mice resulted in improved adipose tissue inflammation in parallel to reduced lysozyme activity. Of note, Lyz2 gene knockdown restored adipogenesis and reduced weight gain in this model. In conclusion, altogether these observations point to lysozyme as a new actor in obesity-associated adipose tissue dysfunction. The therapeutic targeting of lysozyme production might contribute to improve adipose tissue metabolic homeostasis.
  • Autores: Díez Goñi, María de las Nieves (Autor de correspondencia); Pacheco, S.; Llorente Ortega, Marcos; et al.
    Revista: OTOLARYNGOLOGY-HEAD AND NECK SURGERY
    ISSN: 0194-5998 Vol.164 N° 2 2021 págs. 339 - 345
    Resumen
    Objective To validate a simulator for upper airway examination, fitted with sensors, for use as an academic tool for learning how to conduct examination of the upper airway and for evaluation of that learning. Study Design Validation study. Setting Undergraduate medical education. Subjects and Methods A group of 18 fifth-year medical students and another of 6 otorhinolaryngology specialists conducted 6 examinations each with the simulator. To investigate concurrent validity, we calculated the correlation between damage scores provided by the simulator and damage assessment by a specialist. To evaluate construct validity, we compared both groups with regard to damage scores, technical procedure, and time spent. To examine content and face validity, we used questionnaires based on a 5-point Likert scale. Results For concurrent validity, the correlation between the simulator's damage scores and the specialist's damage assessment was high: Spearman's rho was 0.828 (P< .001). For construct validity, the group of students differed from the group of specialists in damage scores (P= .027) and in technical procedures (P< .001) but not in time spent. For content validity, all questionnaire statements were scored highly, and both groups had similar average scores. For face validity, the group of specialists considered the simulator to be realistic, and all statements on the questionnaire were rated with at least 4/5. Conclusion Concurrent, construct, content, and face validity have been demonstrated for a sensor-fitted simulator for upper airway examination, which is therefore accurate enough to be used as an academic tool for learning and evaluation of learning.
  • Autores: Unamuno Iñurritegui, Xabier; Gómez Ambrosi, Javier; Ramírez, B.; et al.
    Revista: CELLULAR AND MOLECULAR IMMUNOLOGY
    ISSN: 1672-7681 Vol.18 N° 4 2021 págs. 1045 - 1057
    Resumen
    The NLRP3-IL-1 beta pathway plays an important role in adipose tissue (AT)-induced inflammation and the development of obesity-associated comorbidities. We aimed to determine the impact of NLRP3 on obesity and its associated metabolic alterations as well as its role in adipocyte inflammation and extracellular matrix (ECM) remodeling. Samples obtained from 98 subjects were used in a case-control study. The expression of different components of the inflammasome as well as their main effectors and inflammation- and ECM remodeling-related genes were analyzed. The impact of blocking NLRP3 using siRNA in lipopolysaccharide (LPS)-mediated inflammation and ECM remodeling signaling pathways was evaluated. We demonstrated that obesity (P < 0.01), obesity-associated T2D (P < 0.01) and NAFLD (P < 0.05) increased the expression of different components of the inflammasome as well as the expression and release of IL-1 beta and IL-18 in AT. We also found that obese patients with T2D exhibited increased (P < 0.05) hepatic gene expression levels of NLRP3, IL1B and IL18. We showed that NLRP3, but not NLRP1, is regulated by inflammation and hypoxia in visceral adipocytes. We revealed that the inhibition of NLRP3 in human visceral adipocytes significantly blocked (P < 0.01) LPS-induced inflammation by downregulating the mRNA levels of CCL2, IL1B, IL6, IL8, S100A8, S100A9, TLR4 and TNF as well as inhibiting (P < 0.01) the secretion of IL1-beta into the culture medium. Furthermore, blocking NLRP3 attenuated (P < 0.01) the LPS-induced expression of important molecules involved in AT fibrosis (COL1A1, COL4A3, COL6A3 and MMP2). These novel findings provide evidence that blocking the expression of NLRP3 reduces AT inflammation with significant fibrosis attenuation.
  • Autores: Fruhbeck Martínez, Gema (Autor de correspondencia); Mentxaka, A.; Ahechu Garayoa, Patricia; et al.
    Revista: JOURNAL OF INFLAMMATION RESEARCH
    ISSN: 1178-7031 Vol.14 2021 págs. 6431 - 6446
    Resumen
    Background: Inflammasomes maintain tissue homeostasis and their altered regulation in the colon, and the adipose tissue (AT) leads to chronic activation of inflammatory pathways promoting colon cancer (CC) development. We aimed to analyze the potential involvement of inflammasomes in obesity-associated CC. Methods: Ninety-nine volunteers [61 with obesity (OB) and 38 normoponderal (NP)] further subclassified according to the approved protocol for the diagnosis of CC (58 without CC and 41 with CC) were included in the case-control study. Results: CC (P<0.01) and obesity (P<0.01) were accompanied by increased mRNA levels of NLRP3, NLRP6, ASC, IL1B and NOD2 in VAT. Contrarily, patients with CC exhibited a downregulation of NLRP6 and IL18 in their colon. Additionally, we revealed that the decreased Nlrp1 (P<0.05), Nlrp3 (P<0.01) and Nlrp6 (P<0.01) mRNA levels in the colon from obese rats significantly increase (P<0.05) after caloric restriction. Adipocyteconditioned media obtained from subjects with obesity reduced (P<0.01) the mRNA of NLRP3 as well as molecules involved in maintaining the intestinal integrity (MUC2, CLDN1 and TJP1) and the anti-inflammatory factors FGF21, KLF4, and IL33 and in HT 29 cells. We also found that the knockdown of NLRP6 in HT-29 cells significantly upregulated (P<0.05) the mRNA of NLRP1 and NLRP3 and inhibited (P<0.05) the expression levels of MUC2. Finally, we showed that the incubation of HT-29 with Akkermansia muciniphila influence (P<0.05) the inflammasome expression profile as well as intestinal integrity-related genes and aberrant inflammation. Conclusions: These findings provide evidence that the downregulated levels of NLRP6 and IL18 in the colon from patients with CC may be responsible for a reduced intestinal-barrier integrity, triggering local inflammation, which in turn acts on the dysfunctional AT in obesity, increasing the expression of different inflammasome components and flaring up a vicious cycle of uncontrollable inflammatory cascades that favours a pro-tumorigenic microenvironment.
  • Autores: Santamaria Sandi, J. (Autor de correspondencia); Navarro González, E.; Herrero Ruiz, A.; et al.
    Revista: ENDOCRINOLOGIA DIABETES Y NUTRICION
    ISSN: 2530-0180 Vol.68 N° 8 2021 págs. 577 - 588
    Resumen
    Endocrinology and Nutrition is a medical specialty covering the study and treatment of diseases of the endocrine system, metabolism and those derived from the nutritional process, including knowledge of diagnostic techniques and dietary and therapeutic measures. In order to develop these activities and plan the management of resources allocated for this purpose, the so-called Portfolio of Services of the specialty has to be defined. A Portfolio of Services is defined as the set of techniques, technologies or procedures through which care services are provided in a healthcare centre, department or institution. It is an essential tool for organization of a hospital Unit or Department by defining the roles and procedures of its healthcare professionals, and also for structuring the resources required to perform the activity. It also allows for defining how to use these resources and identifying the objectives to be achieved, improving the quality of clinical care. Finally, the definition and preparation of the portfolio of services makes it possible to have an inventory of the offer of healthcare services and to detect new healthcare needs. (c) 2021 SEEN y SED. Published by Elsevier Espana, S.L.U. All rights reserved.
  • Autores: Perdomo Zelaya, Carolina María; Gómez Ambrosi, Javier; Becerril Mañas, Sara; et al.
    Revista: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
    ISSN: 1422-0067 Vol.22 N° 23 2021
    Resumen
    Angiopoietin-like protein 8 (ANGPTL8) is an hepatokine altered in several metabolic conditions, such as obesity, type 2 diabetes, dyslipidemia and nonalcoholic fatty liver disease (NAFLD). We sought to explore whether ANGPTL8 is involved in NAFLD amelioration after bariatric surgery in experimental models and patients with severe obesity. Plasma ANGPTL8 was measured in 170 individuals before and 6 months after bariatric surgery. Hepatic ANGPTL8 expression was evaluated in liver biopsies of patients with severe obesity undergoing bariatric surgery with available liver pathology analysis (n = 75), as well as in male Wistar rats with diet-induced obesity subjected to sham operation, sleeve gastrectomy or Roux-en-Y gastric bypass (RYGB) (n = 65). The effect of ANGPTL8 on lipogenesis was assessed in human HepG2 hepatocytes under palmitate-induced lipotoxic conditions. Plasma concentrations and hepatic expression of ANGPTL8 were increased in patients with obesity-associated NAFLD in relation to the degree of hepatic steatosis. Sleeve gastrectomy and RYGB improved hepatosteatosis and reduced the hepatic ANGPTL8 expression in the preclinical model of NAFLD. Interestingly, ANGPTL8 inhibited steatosis and expression of lipogenic factors (PPARG2, SREBF1, MOGAT2 and DGAT1) in palmitate-treated human hepatocytes. Together, ANGPTL8 is involved in the resolution of NAFLD after bariatric surgery partially by the inhibition of lipogenesis in steatotic hepatocytes.
  • Autores: Gómez de Segura, I.; Ahechu Garayoa, Patricia; Gómez Ambrosi, Javier; et al.
    Revista: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
    ISSN: 1422-0067 Vol.22 N° 16 2021 págs. 8485
    Resumen
    Objective: The protein microfibril-associated glycoprotein (MAGP)-1 constitutes a crucial extracellular matrix protein. We aimed to determine its impact on visceral adipose tissue (VAT) remodelling during obesity-associated colon cancer (CC). Methods: Samples obtained from 79 subjects (29 normoponderal (NP) (17 with CC) and 50 patients with obesity (OB) (19 with CC)) were used in the study. Circulating concentrations of MAGP-1 and its gene expression levels (MFAP2) in VAT were analysed. The impact of inflammation-related factors and adipocyte-conditioned media (ACM) on MFAP2 mRNA levels in colon adenocarcinoma HT-29 cells were further analysed. The effects of MAGP-1 in the expression of genes involved in the extracellular matrix (ECM) remodelling and tumorigenesis in HT-29 cells was also explored. Results: Obesity (p < 0.01) and CC (p < 0.001) significantly decreased MFAP2 gene expression levels in VAT whereas an opposite trend in TGFB1 mRNA levels was observed. Increased mRNA levels of MFAP2 after the stimulation of HT-29 cells with lipopolysaccharide (LPS) (p < 0.01) and interleukin (IL)-4 (p < 0.01) together with a downregulation (p < 0.05) after hypoxia mimicked by CoCl2 treatment was observed. MAGP-1 treatment significantly enhanced the mRNA levels of the ECM-remodelling genes collagen type 6 alpha 3 chain (COL6A3) (p < 0.05), decorin (DCN) (p < 0.01), osteopontin (SPP1) (p < 0.05) and TGFB1 (p < 0.05). Furthermore, MAGP-1 significantly reduced (p < 0.05) the gene expression levels of prostaglandin-endoperoxide synthase 2 (COX2/PTGS2), a key gene controlling cell proliferation, growth and adhesion in CC. Interestingly, a significant decrease (p < 0.01) in the mRNA levels of MFAP2 in HT-29 cells preincubated with ACM from volunteers with obesity compared with control media was observed. Conclusion: The decreased levels of MAGP-1 in patients with obesity and CC together with its capacity to modulate key genes involved in ECM remodelling and tumorigenesis suggest MAGP-1 as a link between AT excess and obesity-associated CC development.
  • Autores: Baptista Jardín, Peter Michael (Autor de correspondencia); Martinez Ruiz de Apodaca, P.; Carrasco, M.; et al.
    Revista: JOURNAL OF CLINICAL MEDICINE
    ISSN: 2077-0383 Vol.10 N° 9 2021 págs. 1883
    Resumen
    Study Objectives: Evaluating daytime neuromuscular electrical training (NMES) of tongue muscles in individuals with Primary Snoring and Mild Obstructive Sleep Apnea (OSA). Methods: A multicenter prospective study was undertaken in patients with primary snoring and mild sleep apnea where daytime NMES (eXciteOSA(R) Signifier Medical Technologies Ltd., London W6 0LG, UK) was used for 20 min once daily for 6 weeks. Change in percentage time spent snoring was analyzed using a two-night sleep study before and after therapy. Participants and their bed partners completed sleep quality questionnaires: Epworth Sleepiness Scale (ESS) and Pittsburgh Sleep Quality Index (PSQI), and the bed partners reported on the nighttime snoring using a Visual Analogue Scale (VAS). Results: Of 125 patients recruited, 115 patients completed the trial. Ninety percent of the study population had some reduction in objective snoring with the mean reduction in the study population of 41% (p < 0.001). Bed partner-reported snoring reduced significantly by 39% (p < 0.001). ESS and total PSQI scores reduced significantly (p < 0.001) as well as bed partner PSQI (p = 0.017). No serious adverse events were reported. Conclusions: Daytime NMES (eXciteOSA(R)) is demonstrated to be effective at reducing objective and subjective snoring. It is associated with effective improvement in patient and bed partner sleep quality and patient daytime somnolence. Both objective and subjective measures demonstrated a consistent ...
  • Autores: Dicker, D. (Autor de correspondencia); Alfadda, A. A.; Coutinho, W.; et al.
    Revista: EUROPEAN JOURNAL OF INTERNAL MEDICINE
    ISSN: 0953-6205 Vol.91 2021 págs. 10 - 16
    Resumen
    Background: People with obesity (PwO) often struggle to achieve and maintain weight loss. This can perpetuate and/or be influenced by feelings of low motivation. This analysis from ACTION-IO data identified factors associated with PwO motivation to lose weight. Methods: PwO completed an online survey in 11 countries. Exploratory multinomial logistic regression analyses identified independent variables associated with self-report of feeling motivated versus not motivated to lose weight. Results: Data from 10,854 PwO were included (5,369 motivated; 3,312 neutral; 2,173 not motivated). Variables associated with feeling motivated versus not motivated included (odds ratio [95% confidence interval]): acknowledgement of healthcare professional (HCP) responsibility to contribute to weight loss (2.32 [1.86-2.88]), comfort in talking to their HCP about weight (1.46 [1.24-1.72), agreement that it is easy to lose weight (1.73 [1.30-2.31]), and a goal of reducing risks from excess weight (1.45 [1.22-1.73]). Conversely, if PwO considered obesity less important than other diseases they were less likely to report feeling motivated (0.49 [0.41-0.58]). PwO who reported being motivated to lose weight were more likely to exercise >= 5 times a week versus <1 time a week (2.77 [2.09-3.68]) than those who reported they were not motivated. Conclusions: Positive interactions with HCPs, self-efficacy, setting goals and knowledge of the importance of weight management, in addition to regular exercising, may increase PwO motivation for weight loss. Appropriate HCP support may help PwO who are ready to engage in weight management. Clinical trial registration: : NCT03584191.
  • Autores: Calvete, O. (Autor de correspondencia); Reyes, J.; Valdés-Socin, H.; et al.
    Revista: CELLS
    ISSN: 2073-4409 Vol.10 N° 12 2021 págs. 3500
    Resumen
    Autoimmune polyendocrine syndrome (APS) is assumed to involve an immune system malfunction and entails several autoimmune diseases co-occurring in different tissues of the same patient; however, they are orphans of its accurate diagnosis, as its genetic basis and pathogenic mechanism are not understood. Our previous studies uncovered alterations in the ATPase H+/K+ Transporting Subunit Alpha (ATP4A) proton pump that triggered an internal cell acid-base imbalance, offering an autoimmune scenario for atrophic gastritis and gastric neuroendocrine tumors with secondary autoimmune pathologies. Here, we propose the genetic exploration of APS involving gastric disease to understand the underlying pathogenic mechanism of the polyautoimmune scenario. The whole exome sequencing (WES) study of five autoimmune thyrogastric families uncovered different pathogenic variants in SLC4A2, SLC26A7 and SLC26A9, which cotransport together with ATP4A. Exploratory in vitro studies suggested that the uncovered genes were involved in a pathogenic mechanism based on the alteration of the acid-base balance. Thus, we built a custom gene panel with 12 genes based on the suggested mechanism to evaluate a new series of 69 APS patients. In total, 64 filtered putatively damaging variants in the 12 genes of the panel were found in 54.17% of the studied patients and none of the healthy controls. Our studies reveal a constellation of solute carriers that co-express in the tissues affected with different autoimmune diseases, proposing a unique genetic origin for co-occurring pathologies. These results settle a new-fangled genetics-based mechanism for polyautoimmunity that explains not only gastric disease, but also thyrogastric pathology and disease co-occurrence in APS that are different from clinical incidental findings. This opens a new window leading to the prediction and diagnosis of co-occurring autoimmune diseases and clinical management of patients.
  • Autores: Francque, S. M. (Autor de correspondencia); Marchesini, G.; Kautz, A.; et al.
    Revista: JHEP REPORTS
    ISSN: 2589-5559 Vol.3 N° 5 2021 págs. 100322
    Resumen
    This patient guideline is intended for all patients at risk of or living with non-alcoholic fatty liver disease (NAFLD). NAFLD is the most frequent chronic liver disease worldwide and comes with a high disease burden. Yet, there is a lot of unawareness. Furthermore, many aspects of the disease are still to be unravelled, which has an important impact on the information that is given (or not) to patients. Its management requires a close interaction between patients and their many healthcare providers. It is important for patients to develop a full understanding of NAFLD in order to enable them to take an active role in their disease management. This guide summarises the current knowledge relevant to NAFLD and its management. It has been developed by patients, patient representatives, clinicians and scientists and is based on current scientific recommendations, intended to support patients in making informed decisions.
  • Autores: González-Rellán, M. J.; Fondevila, M. F.; Fernández, U.; et al.
    Revista: NATURE COMMUNICATIONS
    ISSN: 2041-1723 Vol.12 N° 1 2021 págs. 5068
    Resumen
    p53 regulates signalling pathways involved in metabolic homeostasis. Here the authors show that O-GlcNAcylation of p53 in the liver plays a key role in the physiological regulation of glucose homeostasis, potentially via controlling the expression of the gluconeogenic enzyme phosphoenolpyruvate carboxykinase. p53 regulates several signaling pathways to maintain the metabolic homeostasis of cells and modulates the cellular response to stress. Deficiency or excess of nutrients causes cellular metabolic stress, and we hypothesized that p53 could be linked to glucose maintenance. We show here that upon starvation hepatic p53 is stabilized by O-GlcNAcylation and plays an essential role in the physiological regulation of glucose homeostasis. More specifically, p53 binds to PCK1 promoter and regulates its transcriptional activation, thereby controlling hepatic glucose production. Mice lacking p53 in the liver show a reduced gluconeogenic response during calorie restriction. Glucagon, adrenaline and glucocorticoids augment protein levels of p53, and administration of these hormones to p53 deficient human hepatocytes and to liver-specific p53 deficient mice fails to increase glucose levels. Moreover, insulin decreases p53 levels, and over-expression of p53 impairs insulin sensitivity. Finally, protein levels of p53, as well as genes responsible of O-GlcNAcylation are elevated in the liver of type 2 diabetic patients and positively correlate with glucose and HOMA-IR. Overall these results indicate that the O-GlcNAcylation of p53 plays an unsuspected key role regulating in vivo glucose homeostasis.
  • Autores: Llorente Ortega, Marcos; Fernández González, Secundino (Autor de correspondencia)
    Revista: SIMULATION IN HEALTHCARE
    ISSN: 1559-2332 Vol.16 N° 5 2021 págs. 367 - 371
    Resumen
    Introduction: The AirSim Multi (TruCorp) airway simulator is used to practice exploration of the upper respiratory tract with a flexible endoscope to assess the nasal cavities, their structures and spaces (inferior, middle, and superior turbinates and meati), and the nasopharynx. The passage of the flexible endoscope through the nose is usually the most annoying and painful maneuver to continue the exploration of the airway to the pharynx and larynx. For this reason, it is important to develop self-assessment training systems in safe environments that allow trainees to develop the necessary skills to carry out this type of assessment with the least inconvenience and the greatest security. Despite this simulator's accurate anatomical reproduction of the tract, its suitability as a tool for endoscope exploration learning is limited without a feedback system. Effective endoscopic exploration should not cause pain or lesions, not only for comfort and safety reasons, but also because only when discomfort is minimized is a complete and detailed exploration of the anatomical structures possible. The objective of the project was to provide a feedback system from the simulator to the trainee that would facilitate improvements in self-trained skills needed to perform an endoscopic exploration of the airways. Methods: A device based on the Hall-effect sensor was designed and placed outside the airway in the upper nasal turbinate. This device detects changes in the magnetic flux, indicating a displacement on the nasal turbinate due to endoscopic maneuvers that deform the inside of the simulator and would be expected to be harmful or painful in real life. Results: The improved AirSim provides audible and visual feedback during exploration to indicate a change on the nasal turbinate due to endoscopic contact with the turbinate surface that would be expected to be harmful or painful in real life. We expect this feature to facilitate self-learning with minimal professional supervision and reduce the overall training time required to successfully perform a complete exploration of the airway. Conclusions: The inclusion of sensors on a passive simulator is a cost-effective measure that may allow for better training experiences using AirSim Multi simulator from the TruCorp company. Our improved simulator turns endoscopic exploration into a self-assessed exercise suitable for all disciplines and level of learners.
  • Autores: Testa, G.; Mora-Maltas, B.; Camacho-Barcia, L.; et al.
    Revista: NUTRIENTS
    ISSN: 2072-6643 Vol.13 N° 12 2021
    Resumen
    Impulsive and compulsive behaviors have both been observed in individuals with obesity. The co-occurrence of obesity and type 2 diabetes (T2D) is more strongly associated with impulsivity, although there are no conclusive results yet. A multidimensional assessment of impulsivity and compulsivity was conducted in individuals with obesity in the absence or presence of T2D, compared with healthy, normal-weight individuals, with highly impulsive patients (gambling disorders), and with highly compulsive patients (anorexia nervosa). Decision making and novelty seeking were used to measure impulsivity, and cognitive flexibility and harm avoidance were used for compulsivity. For impulsivity, patients with obesity and T2D showed poorer decision-making ability compared with healthy individuals. For compulsivity, individuals with only obesity presented less cognitive flexibility and high harm avoidance; these dimensions were not associated with obesity with T2D. This study contributes to the knowledge of the mechanisms associated with diabetes and its association with impulsive-compulsive behaviors, confirming the hypothesis that patients with obesity and T2D would be characterized by higher levels of impulsivity.
  • Autores: Pomar, M. D. B. (Autor de correspondencia); García, N. V.; Herrera, M. A. R.; et al.
    Revista: ENDOCRINOLOGIA DIABETES Y NUTRICION
    ISSN: 2530-0180 Vol.68 N° 2 2021 págs. 130 - 136
    Resumen
    Obesity is one of the great challenges in healthcare nowadays with important impli-cations for health so requiring comprehensive management. This document aims to establish practical and evidence-based recommendations for the diagnosis and management of in Spain, from the perspective of the clinical endocrinologist. A position statement has been made that can be consulted at www.seen.es, and that has been agreed by the Obesity Group of the Spanish Society of Endocrinology and Nutrition (GOSEEN), together with the Nutrition Area (NutriSEEN) and the Working Group of Endocrinology, Nutrition and Physical Exercise (GENEFSEEN).
  • Autores: Fruhbeck Martínez, Gema
    Revista: EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
    ISSN: 0014-2972 Vol.51 N° Supl. 1 2021 págs. 71
  • Autores: Gonzalez Rellan, M. J.; Fernández Fondevila, M.; Fernández Paz, U.; et al.
    Revista: JOURNAL OF HEPATOLOGY (ONLINE)
    ISSN: 0168-8278 Vol.75 N° Supl. 2 2021 págs. S249 - S250
  • Autores: Chiva San Román, Santiago; Polo-Gay, R.; Muñoz Bastidas, Carmina Alejandra; et al.
    Revista: EUROPEAN UROLOGY
    ISSN: 0302-2838 Vol.79 N° Supl. 1 2021 págs. S1355
  • Autores: Tuero Ojanguren, Carlota (Autor de correspondencia); Valentí Azcarate, Víctor; Rotellar Sastre, Fernando; et al.
    Revista: OBESITY SURGERY
    ISSN: 0960-8923 Vol.30 N° 7 2020 págs. 2763 - 2780
    Resumen
    Since the description of ghrelin in 1999, several studies have dug into the effects of this hormone and its relationship with bariatric surgery. While some aspects are still unresolved, a clear connection between ghrelin and the changes after metabolic surgery have been established. Besides weight loss, a significant amelioration in obesity-related comorbidities following surgery has also been reported. These changes in patients occur in the early postoperative period, before the weight loss appears, so that amelioration may be mainly due to hormonal changes. The purpose of this review is to go through the current body of knowledge of ghrelin's physiology, as well as to update and clarify the changes that take place in ghrelin concentrations following bariatric/metabolic surgery together with their potential consolidation to outcomes.
  • Autores: Donini, L. M. (Autor de correspondencia); Busetto, L.; Bauer, J. M. ; et al.
    Revista: CLINICAL NUTRITION
    ISSN: 0261-5614 Vol.39 N° 8 2020 págs. 2368 - 2388
    Resumen
    Background: Sarcopenic obesity is a clinical and functional condition characterized by the coexistence of excess fat mass and sarcopenia. Currently, different definitions of sarcopenic obesity exist and its diagnostic criteria and cut-offs are not universally established. Therefore, the prevalence and sensitivity of this condition for any disease risk prediction is affected significantly. Aim: This work was conducted under the auspices of the European Society for Clinical Nutrition and Metabolism (ESPEN) and the European Association for the Study of Obesity (EASO). An international expert panel performed a systematic review as an initial step to analyze and summarize the available scientific literature on the definitions and the diagnostic criteria for sarcopenic obesity proposed and/or applied in human studies to date. Methods: The present systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The search was conducted in April 2018 in three databases (PubMed, Scopus, Web of Science). Human studies conducted in both sexes, irrespective of ethnicity, and published from 2007 to 2018 were included; cohorts of individuals with obesity and acute or chronic conditions and treatments reported to negatively influence skeletal muscle mass and function independently of obesity were excluded from final analyses. The quality of the studies was evaluated using the Newcastle-Ottawa Scale (NOS) adapted for cross sectional studies. Results: The electronic search retrieved 2335 papers of which 75 met the eligibility criteria. A marked heterogeneity in definitions and approaches to diagnose sarcopenic obesity was observed. This was mainly due to differences in the definitions of obesity and sarcopenia, in the methodologies used to assess body composition and physical function, and in the reference values for the variables that have been used (different cut-offs, interquartile analysis, diverse statistical stratification methods). This variability may be attributable, at least in part, to the availability of the methodologies in the different settings, to the variability in specialties and backgrounds of the researcher, and to the different settings (general population, clinical settings, etc.) where studies were performed. Conclusion: The results of the current work support the need for consensus proposals on: 1) definition of sarcopenic obesity; 2) diagnostic criteria both at the level of potential gold-standards and acceptable surrogates with wide clinical applicability, and with related cut-off values; 3) methodologies to be used in actions 1 and 2. First steps should be aimed at reaching consensus on plausible proposals that would need subsequent validation based on homogeneous studies and databases, possibly based on analyses of existing cohorts, to help define the prevalence of the condition, its clinical and functional relevance as well as most effective prevention and treatment strategies.
  • Autores: Rodríguez Murueta-Goyena, Amaia (Autor de correspondencia); Becerril Mañas, Sara; Hernandez-Pardos, A. W. ; et al.
    Revista: CURRENT OPINION IN PHARMACOLOGY
    ISSN: 1471-4892 Vol.52 2020 págs. 1 - 8
    Resumen
    White (WAT) and brown (BAT) adipose tissue communicate with skeletal muscle and heart through the secretion of adipokines (adiponectin, leptin, omentin, osteopontin or cardiotrophin-1) and batokines (BMP8b, FGF-21, endothelin-1 or IL-6), respectively. Furthermore, several bioactive lipids termed lipokines [palmitoleate (C16:1n7) or 12,13-diHOME] and microRNAs capsuled in exosomes (miR-27a, miR122, miR-130b, miR-155, miR-200a or miR-320d) secreted from white and brown adipocytes also influence the skeletal and cardiac muscle function. The review focuses on the depot related differences in adipose tissue-derived signals (adipokines, batokines, lipokines and exosomal miRNAs) and their impact on skeletal muscle under physiological conditions as well as in obesity. The relevance of regular physical activity and exercise on fat depot-specific adaptations to improve metabolic health will also be addressed.
  • Autores: Perdomo Zelaya, Carolina María; D'Ingianna , P.; Escalada San Martín, Francisco Javier; et al.
    Revista: POLSKIE ARCHIWUM MEDYCYNY WEWNETRZNEJ-POLISH ARCHIVES OF INTERNAL MEDICINE
    ISSN: 0032-3772 Vol.130 N° 11 2020 págs. 975 - 985
    Resumen
    Nonalcoholic fatty liver disease (NAFLD) is a clinical condition that encompasses various forms of liver damage not caused by chronic alcohol consumption. In the absence of other etiologies, it ranges from steatosis to nonalcoholic steatohepatitis and cirrhosis. The prevalence of NAFLD has considerably increased over the last years owing to the current lifestyle (unhealthy diet and sedentarism). Besides, it is associated with metabolic risk factors such as obesity, arterial hypertension, dyslipidemia, and type 2 diabetes. Given the poor prognosis of patients with advanced NAFLD, a practical therapeutic approach is necessary to halt its natural history. However, no licensed drugs have been approved for this purpose to date. Nowadays, we are in a race to find the first drug able to stop the incidence of NAFLD and reverse the disease in patients at more advanced stages. Meanwhile, the management of the NAFLD metabolic overload, including weight loss, cardiovascular protection, insulin sensitization, and lipid reduction, is the only strategy to improve hepatic and extrahepatic outcomes. In this review, we aimed to describe the management of the main metabolic disorders related to NAFLD, such as type 2 diabetes, arterial hypertension, and dyslipidemia.
  • Autores: van-Hulsteijn, L. T. (Autor de correspondencia); Pasquali, R.; Casanueva, F.; et al.
    Revista: EUROPEAN JOURNAL OF ENDOCRINOLOGY
    ISSN: 0804-4643 Vol.182 N° 1 2020 págs. 11 - 21
    Resumen
    Objective: The increasing prevalence of obesity is expected to promote the demand for endocrine testing. To facilitate evidence guided testing, we aimed to assess the prevalence of endocrine disorders in patients with obesity. The review was carried out as part of the Endocrine Work-up for the Obesity Guideline of the European Society of Endocrinology. Design: Systematic review and meta-analysis of the literature. Methods: A search was performed in MEDLINE, EMBASE, Web of Science and COCHRANE Library for original articles assessing the prevalence of hypothyroidism, hypercortisolism, hypogonadism (males) or hyperandrogenism (females) in patients with obesity. Data were pooled in a random-effects logistic regression model and reported with 95% confidence intervals (95% CI). Results: Sixty-eight studies were included, concerning a total of 19.996 patients with obesity. The pooled prevalence of overt (newly diagnosed or already treated) and subclinical hypothyroidism was 14.0% (95% CI: 9.7-18.9) and 14.6% (95% CI: 9.2-20.9), respectively. Pooled prevalence of hypercortisolism was 0.9% (95% CI: 0.3-1.6). Pooled prevalence of hypogonadism when measuring total testosterone or free testosterone was 42.8% (95% CI: 37.6-48.0) and 32.7% (95% CI: 23.1-43.0), respectively. Heterogeneity was high for all analyses. Conclusions: The prevalence of endocrine disorders in patients with obesity is considerable, although the underlying mechanisms are complex. Given the cross-sectional design of the studies included, no formal distinction between endocrine causes and consequences of obesity could be made.
  • Autores: Valentí Azcarate, Víctor; Álvarez-Cienfuegos Suárez, Francisco Javier (Autor de correspondencia); Becerril Mañas, Sara; et al.
    Revista: REVISTA ESPAÑOLA DE ENFERMEDADES DIGESTIVAS
    ISSN: 1130-0108 Vol.112 N° 3 2020 págs. 229 - 233
    Resumen
    Bariatric-metabolic surgery is the safest, most effective and long-lasting treatment for obesity and its associated co-morbidities, whether they be metabolic (type 2 diabetes, hyperlipidemia non-alcoholic fatty liver disease) or cardiovascular (myocardial infarction, stroke). Due to the obesity pandemic, bariatric-metabolic surgery is the second most frequent intra-abdominal procedure and the gastroenterologist and the surgeon must be aware of the physiologic changes caused by the anatomic reconfiguration following surgery. Among the mechanisms of action, independent of the loss of weight and fat tissue, surgery leads to the release of gut hormones related to carbohydrate metabolism (the rapid and continuous release of insulin), appetite and degree of satiety (glucagon-like peptide 1, peptide Y-Y, grhelin). As a result, indications for surgery have been extended to earlier disease stages. Apart from the neurohormonal effects, changes in the metabolism of biliary acids and the microbiota have also been reported. The aim of this review is to describe the physiologic changes caused by bariatric-metabolic surgery.
  • Autores: Silva Frojan, Camilo (Autor de correspondencia); García Goñi, Marta; Perdomo Zelaya, Carolina María
    Revista: ANALES DEL SISTEMA SANITARIO DE NAVARRA
    ISSN: 1137-6627 Vol.43 N° 3 2020 págs. 435 - 437
  • Autores: Fruhbeck Martínez, Gema; Baker, J. L.; Busetto, L.; et al.
    Revista: OBESITY FACTS
    ISSN: 1662-4025 Vol.13 N° 2 2020 págs. 292 - 296
  • Autores: Weber, M. ; Mera, P.; Casas, J. ; et al.
    Revista: FASEB JOURNAL
    ISSN: 0892-6638 Vol.34 N° 9 2020 págs. 11816 - 11837
    Resumen
    The prevalence of nonalcoholic fatty liver disease (NAFLD) has increased drastically due to the global obesity pandemic but at present there are no approved therapies. Here, we aimed to revert high-fat diet (HFD)-induced obesity and NAFLD in mice by enhancing liver fatty acid oxidation (FAO). Moreover, we searched for potential new lipid biomarkers for monitoring liver steatosis in humans. We used adeno-associated virus (AAV) to deliver a permanently active mutant form of human carnitine palmitoyltransferase 1A (hCPT1AM), the key enzyme in FAO, in the liver of a mouse model of HFD-induced obesity and NAFLD. Expression of hCPT1AM enhanced hepatic FAO and autophagy, reduced liver steatosis, and improved glucose homeostasis. Lipidomic analysis in mice and humans before and after therapeutic interventions, such as hepatic AAV9-hCPT1AM administration and RYGB surgery, respectively, led to the identification of specific triacylglyceride (TAG) specie (C50:1) as a potential biomarker to monitor NAFFLD disease. To sum up, here we show for the first time that liver hCPT1AM gene therapy in a mouse model of established obesity, diabetes, and NAFLD can reduce HFD-induced derangements. Moreover, our study highlights TAG (C50:1) as a potential noninvasive biomarker that might be useful to monitor NAFLD in mice and humans.
  • Autores: Goossens, G. H. (Autor de correspondencia); Dicker, D. ; Farpour-Lambert, N. J.; et al.
    Revista: OBESITY FACTS
    ISSN: 1662-4025 Vol.13 N° 4 2020 págs. 439 - 452
    Resumen
    Accumulating evidence suggests that obesity is a major risk factor for the initiation, progression, and outcomes of coronavirus disease 2019 (COVID-19). The European Association for the Study of Obesity (EASO), as a scientific and medical society dedicated to the promotion of health and well-being, is greatly concerned about the concomitant obesity and COVID-19 pandemics and their impact on health and society at large. In this perspective, we will address the inherent immunological perturbations and alterations in the renin-angiotensin-aldosterone system in patients with obesity and COVID-19, and discuss how these impairments may underlie the increased susceptibility and more detrimental outcomes of COVID-19 in people with obesity. Clearly, this has important implications for preventive measures, vaccination, and future therapeutic strategies to combat COVID-19. Furthermore, we will highlight important knowledge gaps and provide suggestions for future research and recommendations for policy actions. Since many new reports on COVID-19 rapidly appear, the present perspective should be seen as a focus for discussion to drive forward further understanding, research initiatives, and clinical management of COVID-19.
  • Autores: Sanchez, E.; Sanchez, M. ; Betriu, A.; et al.
    Revista: OBESITY FACTS
    ISSN: 1662-4025 Vol.13 N° 1 2020 págs. 29 - 39
    Resumen
    Objective: There is a close relationship between excess adiposity and cardiovascular disease. Although body mass index (BMI) is the most used approach to estimate excess weight, other anthropometric indices have been developed to measure total body and abdominal adiposity. Here, our objective was to assess the usefulness of these anthropometric indices to detect subclinical atheromatous disease. Methods: A cross-sectional study with 6,809 middle-aged subjects (mean age, 57 [53-63] years) with low to moderate cardiovascular risk from the ILERVAS project. Measures of total body fat (BMI, Clinica Universidad de Navarra - Body Adiposity Estimator [CUN-BAE], and Deurenberg's formula) and central adiposity (waist and neck circumferences, conicity index, waist-to-height ratio, Bonora's equation, the A body adiposity index, and body roundness index) were performed in all participants. Bilateral carotid and femoral ultrasound vascular studies allowed the identification of subjects with plaque. -Results: All measured indices were significantly higher in males with subclinical carotid or femoral plaques (p <= 0.021 for all). Also, a positive and significant correlation between all indices and the number of affected territories was found (p <= 0.013 for all). From the ROC analysis, all measurements identified patients with asymptomatic atheromatosis but none of them helped make clinical decisions. Regarding females, the results were less conclusive. Conclusion: Obesity indices are related to subclinical atheromatosis, especially in men, in a large cohort of middle-aged subjects. However, the indices could not detect the presence of arterial plaque, so, when used in isolation, are unlikely to be decisive.
  • Autores: Lujan Colas, Juan; Tuero Ojanguren, Carlota; Landecho Acha, Manuel Fortún; et al.
    Revista: OBESITY SURGERY
    ISSN: 0960-8923 Vol.30 N° 11 2020 págs. 4293 - 4299
    Resumen
    Background Weight loss after bariatric surgery varies among patients. Patients who do not complete long-term follow-up are considered to loose less weight than those with regular follow-up visits. Objective To evaluate the influence of patients' follow-up compliance on long-term excess weight loss (%EWL) and total weight loss (%TWL) after bariatric surgery, comparing results between gastric bypass (GB) and sleeve gastrectomy (SG). Methods Patients with up to 5 years of follow-up data after bariatric surgery were included in this retrospective analysis. Patients were divided in 2 groups: those in group 1 who had attended every scheduled postoperative appointment and those in group 2 who had been lost to follow-up before 1 year and were later contacted by telephone. %EWL and %TWL were compared to determine the possible relationship between type of surgery and regularity of the follow-up. Results A total of 385 patients were included. A significant difference in EWL was observed at 5 years in the SG group (78% for group 1 versus 39% for group 2;p = 0.02) and GB group (75% for group 1 versus 62% for group 2;p = 0.01). No significant differences between surgeries were found when comparing long-term EWL in group 1 patients 77% for SG versus 75% for GB. For group 2 patients, GB achieved greater EWL than SG;p = 0.005. %TWL patients in group 2 showed significant differences in all periods of study (p < 0.05). Conclusion Bariatric surgery patients who attended all scheduled follow-up appointments experienced significantly greater long-term EWL and TWL than those who did not. GB has apparent increased benefits for weight loss in long-term follow-up when compared with SG for patients who did not attend long-term follow-up. Therefore, continued long-term follow-up of bariatric patients should be encouraged to increase postoperative weight loss results.
  • Autores: Fernandez-Aranda, F. (Autor de correspondencia); Munguia, L. ; Mestre-Bach, G. ; et al.
    Revista: EUROPEAN EATING DISORDERS REVIEW
    ISSN: 1072-4133 Vol.28 N° 6 2020 págs. 871 - 883
    Resumen
    Confinement during the COVID-19 pandemic is expected to have a serious and complex impact on the mental health of patients with an eating disorder (ED) and of patients with obesity. The present manuscript has the following aims: (1) to analyse the psychometric properties of the COVID Isolation Eating Scale (CIES), (2) to explore changes that occurred due to confinement in eating symptomatology; and (3) to explore the general acceptation of the use of telemedicine during confinement. The sample comprised 121 participants (87 ED patients and 34 patients with obesity) recruited from six different centres. Confirmatory Factor Analyses (CFA) tested the rational-theoretical structure of the CIES. Adequate goodness-of-fit was obtained for the confirmatory factor analysis, and Cronbach alpha values ranged from good to excellent. Regarding the effects of confinement, positive and negative impacts of the confinement depends of the eating disorder subtype. Patients with anorexia nervosa (AN) and with obesity endorsed a positive response to treatment during confinement, no significant changes were found in bulimia nervosa (BN) patients, whereas Other Specified Feeding or Eating Disorder (OSFED) patients endorsed an increase in eating symptomatology and in psychopathology. Furthermore, AN patients expressed the greatest dissatisfaction and accommodation difficulty with remote therapy when compared with the previously provided face-to-face therapy. The present study provides empirical evidence on the psychometric robustness of the CIES tool and shows that a negative confinement impact was associated with ED subtype, whereas OSFED patients showed the highest impairment in eating symptomatology and in psychopathology.
  • Autores: Salvador Rodríguez, Javier (Autor de correspondencia); Vilarrasa, N.; Poyato, F.; et al.
    Revista: JOURNAL OF CLINICAL MEDICINE
    ISSN: 2077-0383 Vol.9 N° 9 2020 págs. 2834
    Resumen
    The prevalence of obesity is rapidly rising in Spain. The Awareness, Care and Treatment in Obesity Management-An International Observation (ACTION-IO) study (NCT03584191) was an international cross-sectional survey conducted to identify the perceptions, attitudes, behaviors, and barriers to obesity management for people with obesity (PwO) and healthcare professionals (HCPs); results from Spain are presented. In Spain, 1500 PwO (body mass index >= 30 kg/m(2)based on self-reported height and weight) and 306 HCPs (in direct patient care for >= 2 years) completed the survey. Fewer PwO (59%) than HCPs (93%) agreed that obesity is a chronic disease. Most PwO (80%) assumed complete responsibility for their own weight loss, whilst 19% of HCPs placed the responsibility on PwO. One-fifth of PwO stated they began struggling with weight before age 15. The mean delay in discussing weight for the first time with an HCP was 6 years. Only 24% of HCPs thought their patients were motivated to lose weight, whilst 45% of PwO reported being motivated. Of the 67% of PwO who had discussed their weight with an HCP in the last 5 years, 66% had been formally diagnosed with obesity. Our Spanish dataset reveals discrepancies in the perceptions and attitudes between PwO and HCPs, thus highlighting the need to improve education about obesity and its clinical management.
  • Autores: Alligier, M. ; Barres, R. ; Blaak, E. E.; et al.
    Revista: OBESITY FACTS
    ISSN: 1662-4025 Vol.13 N° 1 2020 págs. 1 - 28
    Resumen
    Heterogeneity of interindividual and intraindividual responses to interventions is often observed in randomized, controlled trials for obesity. To address the global epidemic of obesity and move toward more personalized treatment regimens, the global research community must come together to identify factors that may drive these heterogeneous responses to interventions. This project, called OBEDIS (OBEsity Diverse Interventions Sharing - focusing on dietary and other interventions), provides a set of European guidelines for a minimal set of variables to include in future clinical trials on obesity, regardless of the specific endpoints. Broad adoption of these guidelines will enable researchers to harmonize and merge data from multiple intervention studies, allowing stratification of patients according to precise phenotyping criteria which are measured using standardized methods. In this way, studies across Europe may be pooled for better prediction of individuals' responses to an intervention for obesity - ultimately leading to better patient care and improved obesity outcomes.
  • Autores: Fruhbeck Martínez, Gema; Balaguer, I. ; Mendez-Gimenez, L. ; et al.
    Revista: CELLS
    ISSN: 2073-4409 Vol.9 N° 6 2020 págs. 1403
    Resumen
    Aquaporin-11 (AQP11) is expressed in human adipocytes, but its functional role remains unknown. Since AQP11 is an endoplasmic reticulum (ER)-resident protein that transports water, glycerol, and hydrogen peroxide (H2O2), we hypothesized that this superaquaporin is involved in ER stress induced by lipotoxicity and inflammation in human obesity. AQP11 expression was assessed in 67 paired visceral and subcutaneous adipose tissue samples obtained from patients with morbid obesity and normal-weight individuals. We found that obesity and obesity-associated type 2 diabetes increased (p < 0.05) AQP11 mRNA and protein in visceral adipose tissue, but not subcutaneous fat. Accordingly, AQP11 mRNA was upregulated (p < 0.05) during adipocyte differentiation and lipolysis, two biological processes altered in the obese state. Subcellular fractionation and confocal microscopy studies confirmed its presence in the ER plasma membrane of visceral adipocytes. Proinflammatory factors TNF-¿, and particularly TGF-ß1, downregulated (p < 0.05) AQP11 mRNA and protein expression and reinforced its subcellular distribution surrounding lipid droplets. Importantly, the AQP11 gene knockdown increased (p < 0.05) basal and TGF-ß1-induced expression of the ER markers ATF4 and CHOP. Together, the downregulation of AQP11 aggravates TGF-ß1-induced ER stress in visceral adipocytes. Owing to its "peroxiporin" properties, AQP11 overexpression in visceral fat might constitute a compensatory mechanism to alleviate ER stress in obesity.
  • Autores: Vieira da Silva, I.; Cardoso, C.; Mendez-Gimenez, L.; et al.
    Revista: ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
    ISSN: 0003-9861 Vol.691 2020 págs. 108481
    Resumen
    Aquaporins (AQPs) facilitate water and glycerol movement across membranes. AQP7 is the main aquaglyceroporin in pancreatic beta-cells and was proposed to play a role in insulin exocytosis. Although AQP7-null mice display adult-onset obesity, impaired insulin secretion and insulin resistance, AQP7 loss-of-function homozygous mutations in humans do not correlate with obesity nor type-2 diabetes. In addition, AQP12 is upregulated in pancreatitis. However, the implication of this isoform in endocrine pancreas inflammation is still unclear. Here, we investigated AQP7 and AQP12 involvement in cellular and inflammatory processes using RIN-m5F beta cells, a model widely used for their high insulin secretion. AQP7 and AQP12 expression were directly associated with cell proliferation, adhesion and migration. While tumor necrosis factor-alpha (TNF alpha)-induced inflammation impaired AQP7 expression and drastically reduced insulin secretion, lipopolysaccharides (LPS) prompted AQP7 upregulation, and both TNF alpha and LPS upregulated AQP12. Importantly, cells overexpressing AQP12 are more resistant to inflammation, revealing lower levels of proinflammatory markers. Altogether, these data document AQP7 involvement in insulin secretion and AQP12 implication in inflammation, highlighting their fundamental role in pancreatic beta-cell function.
  • Autores: Castillo, A. M.; Valero-Rubira, I.; Burrell Bustos, María Ángela; et al.
    Revista: PLANTS
    ISSN: 2223-7747 Vol.9 N° 11 2020 págs. 1442
    Resumen
    Microspores can be developmentally reprogrammed by the application of different stress treatments to initiate an embryogenic pathway leading to the production of doubled haploid (DH) plants. Epigenetic modifications are involved in cell reprogramming and totipotency in response to stress. To increase microspore embryogenesis (ME) efficiency in bread wheat, the effect of the histone deacetylase inhibitor trichostatin A (TSA) has been examined in two cultivars of wheat with different microspore embryogenesis response. Diverse strategies were assayed using 0-0.4 mu M TSA as a single induction treatment and after or simultaneously with cold or mannitol stresses. The highest efficiency was achieved when 0.4 mu M TSA was applied to anthers for 5 days simultaneously with a 0.7 M mannitol treatment, producing a four times greater number of green DH plants than mannitol. Ultrastructural studies by transmission electron microscopy indicated that mannitol with TSA and mannitol treatments induced similar morphological changes in early stages of microspore reprogramming, although TSA increased the number of microspores with 'star-like' morphology and symmetric divisions. The effect of TSA on the transcript level of four ME marker genes indicated that the early signaling pathways in ME, involving the TaTDP1 and TAA1b genes, may be mediated by changes in acetylation patterns of histones and/or other proteins.
  • Autores: GUARNIERI, Adriano (Autor de correspondencia); Carnero González, Elena María; Bleau, Anne Marie; et al.
    Revista: BMC OPHTHALMOLOGY
    ISSN: 1471-2415 Vol.20 N° 1 2020 págs. 12
    Resumen
    BackgroundTear film stability is the key event in ocular surface diseases. The purpose of this study is to evaluate spatial and temporal progression of the tear film breakup using an automatic non-invasive device.MethodsNon-invasive tear breakup time (NITBUT) parameters, such as First NITBUT (F-NITBUT) and Average NITBUT (A-NITBUT), were evaluated in 132 glaucoma and 87 control eyes with the Keratograph 5M device. Further analysis of this data was used to determine size, location and progression of tear film breakup with automatically identified breakup areas (BUA). The progression from First BUA (F-BUA) to total BUA (T-BUA) was expressed as Dry Area Growth Rate (DAGR). Differences between both groups were analysed using Student t-test for parametric data and Mann-Whitney U test for non-parametric data. Pearson's correlation coefficient was used to assess the relationship between parametric variables and Spearman in the case of non-parametric variables.ResultsF-NITBUT was 11.437.83s in the control group and 8.17 +/- 5.73 in the glaucoma group (P=0.010). A-NITBUT was 14.04 +/- 7.21 and 11.82 +/- 6.09s in control and glaucoma groups, respectively (P=0.028). F-BUA was higher in the glaucoma group than in the control group (2.73 and 2.28; P=0.022) and was more frequently located at the centre of the cornea in the glaucoma group (P=0.039). T-BUA was also higher in the glaucoma group than in the control group (13.24 and 9.76%; P=0.012) and the DAGR was steeper in the glaucoma group than in the control group (34.38 degrees and 27.15 degrees; P=0.009).Conclusions Shorter NITBUT values and bigger, more central tear film breakup locations were observed in the glaucoma group than in the control group. The DAGR indicates that tear film rupture is bigger and increases faster in glaucomatous eyes than in normal eyes.
  • Autores: Unamuno Iñurritegui, Xabier; Gómez Ambrosi, Javier; Ramirez, B.; et al.
    Revista: JOURNAL OF CLINICAL MEDICINE
    ISSN: 2077-0383 Vol.9 N° 4 2020 págs. 1069
    Resumen
    Compelling evidence suggests that dermatopontin (DPT) regulates collagen and fibronectin fibril formation, the induction of cell adhesion and the prompting of wound healing. We aimed to evaluate the role of DPT on obesity and its associated metabolic alterations as well as its impact in visceral adipose tissue (VAT) inflammation and extracellular matrix (ECM) remodelling. Samples obtained from 54 subjects were used in a case-control study. Circulating and VAT expression levels of DPT as well as key ECM remodelling- and inflammation-related genes were analysed. The effect of pro- and anti-inflammatory mediators on the transcript levels of DPT in visceral adipocytes was explored. The impact of DPT on ECM remodelling and inflammation pathways was also evaluated in cultured adipocytes. We show that obesity and obesity-associated type 2 diabetes (T2D) increased (p < 0.05) circulating levels of DPT. In this line, DPT mRNA in VAT was increased (p < 0.05) in obese patients with and without T2D. Gene expression levels of DPT were enhanced (p < 0.05) in human visceral adipocytes after the treatment with lipopolysaccharide, tumour growth factor (TGF)-beta and palmitic acid, whereas a downregulation (p < 0.05) was detected after the stimulation with interleukin (IL)-4 and IL-13, critical cytokines mediating anti-inflammatory pathways. Additionally, we revealed that DPT increased (p < 0.05) the expression of ECM- (COL6A3, ELN, MMP9, TNMD) and inflammation-related factors (IL6, IL8, TNF) in human visceral adipocytes. These findings provide, for the first time, evidence of a novel role of DPT in obesity and its associated comorbidities by influencing AT remodelling and inflammation.
  • Autores: Fruhbeck Martínez, Gema; Fernandez-Quintana, B. ; Paniagua, M.; et al.
    Revista: METABOLISM-CLINICAL AND EXPERIMENTAL
    ISSN: 0026-0495 Vol.108 2020 págs. 154261
    Resumen
    Background: Fibronectin type IIIdomain-containing protein 4 (FNDC4) constitutes a secreted factor showing a high homology in the fibronectin type III and transmembrane domains with the exercise-associated myokine irisin (FNDC5). We sought to evaluate whether FNDC4 mimics the anti-obesity effects of FNDC5/irisin in human adipose tissue. Methods: Plasma and adipose tissue samples of 78 patients with morbid obesity undergoing bariatric surgery and 26 normal-weight individuals were used in the present study. Results: Plasma FNDC4 was decreased in patients with morbid obesity, related to obesity-associated systemic inflammation and remained unchanged six months after bariatric surgery. Visceral adipose tissue from patients with morbid obesity showed higher expression of FNDC4 and its putative receptor GPR116 regardless of the degree of insulin resistance. FNDC4 content was regulated by lipogenic, lipolytic and proinflammatory stimuli in human visceral adipocytes. FNDC4 reduced intracytosolic lipid accumulation and stimulated a brown-like pattern in human adipocytes, as evidenced by an upregulated expression of UCP-1 and the brown/beige adipocyte markers PRDM16, TMEM26 and CD137. Moreover, FNDC4 treatment upregulated mitochondrial DNA content and factors involved in mitochondrial biogenesis (TFAM, NRF1 and NRF2). Human FNDC4-knockdown adipocytes exhibited an increase in lipogenesis and a reduction of brown/beige-specific fat markers as well as factors involved in mitochondrial biogenesis. Conclusions: Taken together, the novel adipokine FNDC4 reduces lipogenesis and increases fat browning in human visceral adipocytes. The upregulation of FNDC4 in human visceral fat might constitute an attempt to attenuate the adipocyte hypertrophy, inflammation and impaired beige adipogenesis in the obese state.
  • Autores: Hurtado Pardo, Luis; Álvarez-Cienfuegos Suárez, Francisco Javier; Antoñanzas Pérez, Javier; et al.
    Revista: REVISTA ESPAÑOLA DE ENFERMEDADES DIGESTIVAS
    ISSN: 1130-0108 Vol.112 N° 2 2020 págs. 85 - 89
    Resumen
    Objective: the objective of the present study was to analyze the characteristics of resected incidental lesions of the pancreas. Material and methods: a retrospective study was performed of pancreatectomies due to incidentalomas between 1995 and 2018. Results: one hundred pancreatectomies were performed due to incidental lesions; 64 (64%) were solid and 36 (36%) were cystic lesions. The cytological analysis agreed with the diagnosis in 67/71 (88.7%) cases. Thirty-six tumors were cystic, 48 were neuroendocrine and 16 were adenocarcinomas. Disease-free survival for patients with cystic, neuroendocrine tumors and adenocarcinomas was 100%, 79% and 57.7% (p < 0.04). Conclusion: pancreatic incidentalomas have a heterogeneous phenotype and should be treated in experienced centers
  • Autores: Ahechu Garayoa, Patricia; Rotellar Sastre, Fernando; Valentí Azcarate, Víctor (Autor de correspondencia)
    Revista: OBESITY SURGERY
    ISSN: 0960-8923 Vol.30 N° 10 2020 págs. 4127 - 4128
  • Autores: Ezquerro, S.; Becerril Mañas, Sara; Tuero, C.; et al.
    Revista: INTERNATIONAL JOURNAL OF OBESITY
    ISSN: 0307-0565 Vol.44 N° 2 2020 págs. 475 - 487
    Resumen
    BACKGROUND/OBJECTIVES: Bariatric surgery improves nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH), but the underlying mechanisms remain elusive. We evaluated the potential role of ghrelin isoforms in the amelioration of hepatic inflammation after sleeve gastrectomy and Roux-en-Y gastric bypass (RYGB). SUBJECTS/METHODS: Plasma ghrelin isoforms were measured in male Wistar rats (n¿=¿129) subjected to surgical (sham operation, sleeve gastrectomy, or RYGB) or dietary interventions [fed ad libitum a normal (ND) or a high-fat diet (HFD) or pair-fed diet]. The effect of acylated and desacyl ghrelin on markers of inflammation, mitochondrial dysfunction, and endoplasmic reticulum (ER) stress in primary rat hepatocytes under palmitate-induced lipotoxic conditions was assessed. RESULTS: Plasma desacyl ghrelin was decreased after sleeve gastrectomy and RYGB, whereas the acylated/desacyl ghrelin ratio was augmented. Both surgeries diminished obesity-associated hepatic steatosis, CD68+- and apoptotic cells, proinflammatory JNK activation, and Crp, Tnf, and Il6 transcripts. Moreover, a postsurgical amelioration in the mitochondrial DNA content, oxidative phosphorylation (OXPHOS) complexes I and II, and ER stress markers was observed. Specifically, following bariatric surgery GRP78, spliced XBP-1, ATF4, and CHOP levels were reduced, as were phosphorylated eIF2¿. Interestingly, acylated and desacyl ghrelin inhibited steatosis and inflammation of palmitate-treated hepatocytes in parallel to an upregulation of OXPHOS complexes II, III, and V, and a downregulation of ER stress transducers IRE1¿, PERK, ATF6, their downstream effectors, ATF4 and CHOP, as well as chaperone GRP78. CONCLUSIONS: Our data suggest that the increased relative acylated ghrelin levels after bariatric surgery might contribute to mitigate obesity-associated hepatic inflammation, mitochondrial dysfunction, and ER stress.
  • Autores: Fernández González, Secundino; Garaycochea Mendoza del Solar, Octavio (Autor de correspondencia); Martinez-Arellano, A.; et al.
    Revista: JOURNAL OF SPEECH LANGUAGE AND HEARING RESEARCH
    ISSN: 1092-4388 Vol.63 N° 7 2020 págs. 2177 - 2184
    Resumen
    Objective: The aims of this study were to test the hypothesis that greater supraglottic compression (anteroposterior or lateral) correlates with higher subglottic pressure (SGP) and to develop a classification of muscle tension dysphonia (MTD), based on the degree of supraglottic compression during speech. Method: A prospective, cross-sectional study was conducted in a series of 37 consecutive patients diagnosed with MTD with an altered aerodynamic profile characterized by high SGP (more than 90 mmH(2)O). Supraglottic anteroposterior and lateral compression were categorized in three grades and assessed during the laryngoscopic examination. All patients completed the Spanish Voice Handicap Index (VHI) questionnaire and completed an acoustic and aerodynamic voice assessment. The relationship between compression grade and VHI with SGP was analyzed. Results: More than 90% of patients demonstrated some degree of anteroposterior compression, and 67% had some degree of lateral compression. The mean (SD) SGP was 111.03 (16.7) mmH(2)O, and the mean VHI was 27.86 (12.5). The degree of SGP was statistically different in the different grades of anteroposterior compression, and also anteroposterior compression correlated with an SGP (p < .05). The degree of lateral compression was not correlated with SGP. Neither the degree of anteroposterior or lateral compression nor the value of SGP was found to correlate with VHI. Conclusions: Because grade of anteroposterior compression correlates with SGP, these grades can be used for diagnosis and follow-up of MTD patients. To this end and on this basis, we propose a new classification for MTD. Unlike the established classification, our proposed one makes it possible to combine different laryngoscopic features, improving the description of the larynx during phonation.
  • Autores: Escalada San Martín, Francisco Javier (Autor de correspondencia); Bonnet, F.; Wu, J. ; et al.
    Revista: ADVANCES IN THERAPY
    ISSN: 0741-238X Vol.37 N° 9 2020 págs. 3863 - 3877
    Resumen
    Introduction Randomized controlled trials and real-world data from the USA have shown similar glycemic control with insulin glargine 300 U/ml (Gla-300) and insulin glargine 100 U/ml (Gla-100) and reduced hypoglycemia risk with Gla-300. This real-world study describes the efficacy and safety of Gla-300 and Gla-100 in patients with type 2 diabetes (T2D) in France, Spain, and Germany. Methods This retrospective chart review analysis used anonymized data for adults with T2D switching basal insulin analog (BIA) therapy to Gla-300 or Gla-100, or insulin-naive patients initiating Gla-300 or Gla-100. Outcomes included change from baseline to 6-month follow-up in glycated hemoglobin A1c (A1C), total and severe hypoglycemia incidences and events, insulin dose, and reasons for BIA choice. Results Six hundred sixty-five physicians (33.8% Spain, 31.7% France, 34.4% Germany) provided chart data for patients switching to Gla-300 (n = 679) or Gla-100 (n = 429) or initiating Gla-300 (n = 719) or Gla-100 (n = 711). After adjustment for baseline characteristics, A1C reductions from baseline were similar for patients switching to Gla-300 or Gla-100 (- 0.87% vs. - 0.93%;p = 0.326) while those switched to Gla-300 vs. Gla-100 had a significantly greater mean reduction in hypoglycemic events (- 1.29 vs. - 0.81 events during 6 months;p = 0.012). Mean insulin doses after titration were 0.43 +/- 0.36 and 0.40 +/- 0.28 U/kg in Gla-300 and Gla-100 switchers, respectively. Factors that significantly influenced BIA choice included a lower risk of hypoglycemia (for Gla-300) and physician familiarity (for Gla-100). Outcomes for insulin-naive patients were broadly similar to those of switchers. Conclusions In this real-world European study, patients with T2D who switched therapy to Gla-300 or Gla-100 had improved glycemic control and reduced hypoglycemia at 6 months, with significant hypoglycemia advantages with Gla-300.
  • Autores: Dicker, D. (Autor de correspondencia); Bettini, S.; Farpour-Lambert, N. ; et al.
    Revista: OBESITY FACTS
    ISSN: 1662-4025 Vol.13 N° 4 2020 págs. 430 - 438
    Resumen
    The World Health Organization declared COVID-19, the infectious disease caused by the coronavirus SARS-CoV-2, a pandemic on March 12, 2020. COVID-19 is causing massive health problems and economic suffering around the world. The European Association for the Study of Obesity (EASO) promptly recognised the impact that the outbreak could have on people with obesity. On one side, emerging data suggest that obesity represents a risk factor for a more serious and complicated course of COVID-19 in adults. On the other side, the health emergency caused by the outbreak diverts attention from the prevention and care of non-communicable chronic diseases to communicable diseases. This might be particularly true for obesity, a chronic and relapsing disease frequently neglected and linked to significant bias and stigmatization. The Obesity Management Task Force (OMTF) of EASO contributes in this paper to highlighting the key aspects of these two sides of the coin and suggests some specific actions.
  • Autores: Pasquali, R. (Autor de correspondencia); Casanueva, F.; Haluzík, M.; et al.
    Revista: EUROPEAN JOURNAL OF ENDOCRINOLOGY
    ISSN: 0804-4643 Vol.182 N° 1 2020 págs. G1 - G32
    Resumen
    Obesity is an emerging condition, with a prevalence of -20%. Although the simple measurement of BMI is likely a simplistic approach to obesity, BMI is easily calculated, and there are currently no data showing that more sophisticated methods are more useful to guide the endocrine work-up in obesity. An increased BMI leads to a number of hormonal changes. Additionally, concomitant hormonal diseases can be present in obesity and have to be properly diagnosed - which in turn might be more difficult due to alterations caused by body fatness itself. The present European Society of Endocrinology Clinical Guideline on the Endocrine Work-up in Obesity acknowledges the increased prevalence of many endocrine conditions in obesity. It is recommended to test all patients with obesity for thyroid function, given the high prevalence of hypothyroidism in obesity. For hypercortisolism, male hypogonadism and female gonadal dysfunction, hormonal testing is only recommended if case of clinical suspicion of an underlying endocrine disorder. The guideline underlines that weight loss in obesity should be emphasized as key to restoration of hormonal imbalances and that treatment and that the effect of treating endocrine disorders on weight loss is only modest.
  • Autores: Lara, J. P.; Compañ, A.; Vargas, J. A.; et al.
    Revista: EDUCACION MEDICA
    ISSN: 1575-1813 Vol.21 N° 6 2020 págs. 397 - 402
    Resumen
    En este documento se refieren las bases legales nacionales y, más en concreto, las autonómicas andaluzas que dan respaldo a la figura del profesor contratado doctor vinculado y a la posibilidad de convocar las plazas correspondientes en las facultades de medicina de las universidades públicas españolas. Se exponen, asimismo, las características asistenciales y académicas que deben darse para llevar a cabo la convocatoria pública de dichas plazas. Se resume, a continuación, cuál es la situación actual existente en relación con dicha figura del profesorado en las facultades de medicina españolas. Se analizan también las ventajas y las posibles limitaciones que actualmente se derivan de contar con profesores contratados doctores vinculados y ello tanto para los médicos especialistas eventualmente interesados en optar a una de estas plazas como para el centro sanitario y la facultad de medicina correspondientes. Finalmente, se reseña la posible utilidad del documento elaborado por la Conferencia Nacional de Decanos de Facultades de Medicina de España (CNDFME) en la Asamblea General que se celebró en la Facultad de Medicina de Oviedo del 17 al 19 de mayo del 2018 y actualizado en marzo de 2020.
  • Autores: Unamuno Iñurritegui, Xabier; Gómez Ambrosi, Javier; Ramirez, B. ; et al.
    Revista: EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
    ISSN: 0014-2972 Vol.50 2020 págs. 13 - 14
  • Autores: Llorente Gómez de Segura, Ignacio; Catalán Goñi, Victoria; Gómez Ambrosi, Javier; et al.
    Revista: EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
    ISSN: 0014-2972 Vol.50 2020 págs. 12 - 13
  • Autores: Perdomo Zelaya, Carolina María; Fruhbeck Martínez, Gema; Escalada San Martín, Francisco Javier (Autor de correspondencia)
    Revista: NUTRIENTS
    ISSN: 2072-6643 Vol.11 N° 3 2019 págs. 677
    Resumen
    Non-alcoholic fatty liver disease (NAFLD) is a major global health threat due to its growing incidence and prevalence. It is becoming the leading cause of liver disease in addition to its strong association with cardio-metabolic disease. Therefore, its prevention and treatment are of strong public interest. Therapeutic approaches emphasize lifestyle modifications including physical activity and the adoption of healthy eating habits that intend to mainly control body weight and cardio-metabolic risk factors associated with the metabolic syndrome. Lifestyle interventions may be reinforced by pharmacological treatment in advanced stages, though there is still no registered drug for the specific treatment of NAFLD. The purpose of this review is to assess the evidence available regarding the impact of dietary recommendations against NAFLD, highlighting the effect of macronutrient diet composition and dietary patterns in the management of NAFLD.
  • Autores: Di Ciaula, A.; Garruti, G. ; Fruhbeck Martínez, Gema; et al.
    Revista: CURRENT MEDICINAL CHEMISTRY
    ISSN: 0929-8673 Vol.26 N° 19 2019 págs. 3620 - 3638
    Resumen
    Cholesterol gallstone disease is a major health problem in Westernized countries and depends on a complex interplay between genetic factors, lifestyle and diet, acting on specific pathogenic mechanisms. Overweigh, obesity, dyslipidemia, insulin resistance and altered cholesterol homeostasis have been linked to increased gallstone occurrence, and several studies point to a number of specific nutrients as risk- or protective factors with respect to gallstone formation in humans. There is a rising interest in the identification of common and modifiable dietetic factors that put the patients at risk of gallstones or that are able to prevent gallstone formation and growth. In particular, dietary models characterized by increased energy intake with highly refined sugars and sweet foods, high fructose intake, low fiber contents, high fat, consumption of fast food and low vitamin C intake increase the risk of gallstone formation. On the other hand, high intake of monounsaturated fats and fiber, olive oil and fish (omega-3 fatty acids) consumption, vegetable protein intake, fruit, coffee, moderate alcohol consumption and vitamin C supplementation exert a protective role. The effect of some confounding factors (e.g., physical activity) cannot be ruled out, but general recommendations about the multiple beneficial effects of diet on cholesterol gallstones must be kept in mind, in particular in groups at high risk of gallstone formation.
  • Autores: Becerril Mañas, Sara; Rodríguez Murueta-Goyena, Amaia; Catalán Goñi, Victoria; et al.
    Revista: NUTRIENTS
    ISSN: 2072-6643 Vol.11 N° 9 2019 págs. 2129
    Resumen
    Leptin, the product of the ob gene, was originally described as a satiety factor, playing a crucial role in the control of body weight. Nevertheless, the wide distribution of leptin receptors in peripheral tissues supports that leptin exerts pleiotropic biological effects, consisting of the modulation of numerous processes including thermogenesis, reproduction, angiogenesis, hematopoiesis, osteogenesis, neuroendocrine, and immune functions as well as arterial pressure control. Nitric oxide (NO) is a free radical synthesized from L-arginine by the action of the NO synthase (NOS) enzyme. Three NOS isoforms have been identified: the neuronal NOS (nNOS) and endothelial NOS (eNOS) constitutive isoforms, and the inducible NOS (iNOS). NO mediates multiple biological effects in a variety of physiological systems such as energy balance, blood pressure, reproduction, immune response, or reproduction. Leptin and NO on their own participate in multiple common physiological processes, with a functional relationship between both factors having been identified. The present review describes the functional relationship between leptin and NO in different physiological processes.
  • Autores: Martinez, S. B. (Autor de correspondencia); Jauregui, E. P.; Escalada San Martín, Francisco Javier
    Revista: ENDOCRINOLOGIA DIABETES Y NUTRICION
    ISSN: 2530-0180 Vol.66 N° 1 2019 págs. 62 - 68
    Resumen
    The important prevalence and morbidity of obesity has generated an increase in bariatric surgery. It has a positive effect in obesity-related comorbidities. However, it's detrimental to bone health. The underline pathophysiological mechanisms are complex and heterogeneous. The knowledge of these factors may lead us to develop an adequate therapeutic intervention.
  • Autores: James, W. P. T. (Autor de correspondencia); Johnson, R. J.; Speakman, J. R.; et al.
    Revista: JOURNAL OF INTERNAL MEDICINE
    ISSN: 0954-6820 Vol.285 N° 5 2019 págs. 533 - 549
    Resumen
    Our understanding of human evolution has improved rapidly over recent decades, facilitated by large-scale cataloguing of genomic variability amongst both modern and archaic humans. It seems clear that the evolution of the ancestors of chimpanzees and hominins separated 7-9million years ago with some migration out of Africa by the earlier hominins; Homo sapiens slowly emerged as climate change resulted in drier, less forested African conditions. The African populations expanded and evolved in many different conditions with slow mutation and selection rates in the human genome, but with much more rapid mutation occurring in mitochondrial DNA. We now have evidence stretching back 300000years of humans in their current form, but there are clearly four very different large African language groups that correlate with population DNA differences. Then, about 50000-100000years ago a small subset of modern humans also migrated out of Africa resulting in a persistent signature of more limited genetic diversity amongst non-African populations. Hybridization with archaic hominins occurred around this time such that all non-African modern humans possess some Neanderthal ancestry and Melanesian populations additionally possess some Denisovan ancestry. Human populations both within and outside Africa also adapted to diverse aspects of their local environment including altitude, climate, UV exposure, diet and pathogens, in some cases leaving clear signatures of patterns of genetic variation. Notable examples include haemoglobin changes conferring resistance to malaria, other immune changes and the skin adaptations favouring the synthesis of vitamin D. As humans migrated across Eurasia, further major mitochondrial changes occurred with some interbreeding with ancient hominins and the development of alcohol intolerance. More recently, an ability to retain lactase persistence into adulthood has evolved rapidly under the environmental stimulus of pastoralism with the ability to husband lactating ruminants. Increased amylase copy numbers seem to relate to the availability of starchy foods, whereas the capacity to desaturase and elongate monounsaturated fatty acids in different societies seems to be influenced by whether there is a lack of supply of readily available dietary sources of long-chain polyunsaturated fatty acids. The process of human evolution includes genetic drift and adaptation to local environments, in part through changes in mitochondrial and nuclear DNA. These genetic changes may underlie susceptibilities to some modern human pathologies including folate-responsive neural tube defects, diabetes, other age-related pathologies and mental health disorders.
  • Autores: Gargallo Vaamonde, Javier; Fruhbeck Martínez, Gema; Salvador Rodríguez, Javier
    Revista: CURRENT OPINION IN ENDOCRINE AND METABOLIC RESEARCH
    ISSN: 2451-9650 Vol.4 2019 págs. 75 - 82
    Resumen
    Recently marketed antiobesity medications have improved the obesity therapeutic performance by promoting weight loss in patients treated with diet, physical activity and nutritional education. However, mean placebo-subtracted weight loss following treatment with phentermine, lorcaserin, liraglutide 3 mg or the combinations phentermine-topiramate and naltrexone-bupropion reaches 3¿10%. Although this weight reduction translates into significant benefits in obesity comorbidities management, more weight reduction is needed to reduce the gap between conventional treatment and bariatric surgery. The new weekly GLP-1 receptor agonist, semaglutide, exhibits a powerful effect on body weight reduction showing better performance when compared with other members of the same family in diabetic patients. Biochemical engineering has produced diverse unimolecular peptides displaying GLP-1, glucagon and GIP agonist action that are being investigated in preclinical models and clinical trials, showing encouraging results regarding weight loss and treatment of obese comorbidities such as diabetes, dyslipidemia and liver steatosis. Other medications such as amylin analogs, and different agonists and antagonists of satiating and orexigenic neuronal pathways offer new approaches. The possibility of conjugating peptides such as GLP-1 or glucagon with glucocorticoids, estrogens or triiodothyronine to deliver selectively these hormones to tissues expressing receptors involved in energy balance control opens a new era in obesity therapy. Preclinical studies show that this targeting strategy allows achieving selective hormonal actions with prevention of adverse effects in other organs. Peripheral pharmacological approaches including stimulation of thermogenesis, activation of bile acid receptors, lipolysis stimulation and manipulation of gut microbiota may also take part of this unlimited universe of pharmacological options. Drug combinations of compounds acting on different pathways and through diverse mechanisms represent an excellent option to increase efficacy and improve long-term results when compared with strategies based in monotherapy.
  • Autores: Pérez Pevida, Belén (Autor de correspondencia); Escalada San Martín, Francisco Javier; Miras, A. D.; et al.
    Revista: FRONTIERS IN ENDOCRINOLOGY
    ISSN: 1664-2392 Vol.10 2019
    Resumen
    Type 2 diabetes prevalence is increasing dramatically worldwide. Metabolic surgery is the most effective treatment for selected patients with diabetes and/or obesity. When compared to intensive medical therapy and lifestyle intervention, metabolic surgery has shown superiority in achieving glycemic improvement, reducing number of medications and cardiovascular risk factors, which translates in long-term benefits on cardiovascular morbidity and mortality. The mechanisms underlying diabetes improvement after metabolic surgery have not yet been clearly understood but englobe a complex interaction among improvements in beta cell function and insulin secretion, insulin sensitivity, intestinal gluconeogenesis, changes in glucose utilization, and absorption by the gut and changes in the secretory pattern and morphology of adipose tissue. These are achieved through different mediators which include an enhancement in gut hormones release, especially, glucagon-like peptide 1, changes in bile acids circulation, gut microbiome, and glucose transporters expression. Therefore, this review aims to provide a comprehensive appraisal of what is known so far to better understand the mechanisms through which metabolic surgery improves glycemic control facilitating future research in the field.
  • Autores: Yarnoz-Esquiroz, P. (Autor de correspondencia); Lacasa Arregui, Carlos; Riestra, M. ; et al.
    Revista: EUROPEAN EATING DISORDERS REVIEW
    ISSN: 1072-4133 Vol.27 N° 6 2019 págs. 581 - 602
    Resumen
    Objective The aim of this review is to analyse the studies about cost and clinical implications that malnutrition causes in the Spanish hospitals. Material and methods The review of the literature was carried out through a bibliographic search in Web of Science following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria and analyse the cost of treatment of malnourished and anorexia nervosa (AN) patients Results Seventeen studies with economic data related to malnutrition were included. The employment of a nutritional screening is the first tool to determinate the prevalence. Malnutrition is related to an incremental cost due to a longer hospital stay, expensive treatment, and higher rate of readmissions. Malnourished patients present more clinical complications, more infections, and higher mortality. No studies were found with economic data of AN in Spain. Conclusions The prevalence of malnutrition is over 20%, with the elderly patients being the most affected. Nutritional screening is not implanted in all Spanish hospitals in spite of its proven cost-effectiveness. The cost and the clinical implications of malnutrition make this disease a health national problem. The knowledge of the real cost of AN treatment would increase the interest of public institutions on the development of specific Nutritional Screening tools for an early detection of AN.
  • Autores: Landecho Acha, Manuel Fortún; Tuero Ojanguren, Carlota; Valentí Azcarate, Víctor; et al.
    Revista: NUTRIENTS
    ISSN: 2072-6643 Vol.11 N° 11 2019 págs. 2664
    Resumen
    Obesity, which is a worldwide epidemic, confers increased risk for multiple serious conditions including type 2 diabetes, nonalcoholic fatty liver disease, and cardiovascular diseases. Adipose tissue is considered one of the largest endocrine organs in the body as well as an active tissue for cellular reactions and metabolic homeostasis rather than an inert tissue only for energy storage. The functional pleiotropism of adipose tissue relies on its ability to synthesize and release a large number of hormones, cytokines, extracellular matrix proteins, and growth and vasoactive factors, which are collectively called adipokines known to influence a variety of physiological and pathophysiological processes. In the obese state, excessive visceral fat accumulation causes adipose tissue dysfunctionality that strongly contributes to the onset of obesity-related comorbidities. The mechanisms underlying adipose tissue dysfunction include adipocyte hypertrophy and hyperplasia, increased inflammation, impaired extracellular matrix remodeling, and fibrosis together with an altered secretion of adipokines. This review describes the relevance of specific adipokines in the obesity-associated cardiovascular disease.
  • Autores: Paslakis, G.; Aguera, Z. ; Granero, R.; et al.
    Revista: MOLECULAR AND CELLULAR ENDOCRINOLOGY
    ISSN: 0303-7207 Vol.497 2019
    Resumen
    Anorexia nervosa (AN) is a severe eating disorder accompanied by alterations in endocrinological circuits and deficits in neuropsychological performance. In this study, a series of appetite-regulating hormones (ghrelin, leptin, cholecystokinin, PYY, adiponectin, and visfatin) were measured under fasting conditions in female patients with AN and female healthy controls. All of the participants also underwent a battery of neuropsychological assessment [namely the Iowa Gambling Task (IGT), the Wisconsin Card Sorting Test (WCST), and the Stroop Color and Word Test (SCWT)]. As the main finding, we found that higher ghrelin levels predict better performance in the IGT. Ghrelin may be a putative mediator of decision-making, a finding that has not been described so far. The role of ghrelin in decision-making can only be described as speculative, as there are hardly any additional evidence-based data published up to date. Further studies are warranted.
  • Autores: Ezquerro Ezquerro, Silvia; Rodríguez Murueta-Goyena, Amaia; Portincasa, P.; et al.
    Revista: CURRENT MEDICINAL CHEMISTRY
    ISSN: 0929-8673 Vol.26 N° 19 2019 págs. 3593 - 3612
    Resumen
    Background: Obesity is a major health problem that has become a global epidemic. Overweight and obesity are commonly associated with the development of several pathologies, such as insulin resistance, cardiovascular diseases, sleep apnea and several types of cancer, which can lead to further morbidity and mortality. An increased abdominal adiposity renders overweight and obese individuals more prone to metabolic and cardiovascular problems. Objective: This Review aims to describe the dietary strategies to deal with excess adiposity given the medical, social and economic consequences of obesity. Methods: One hundred and eighty-five papers were included in the present Review. Results: Excess adiposity leads to several changes in the biology, morphology and function of the adipose tissue, such as adipocyte hypertrophy and hyperplasia, adipose tissue inflammation and fibrosis and an impaired secretion of adipokines, contributing to the onset of obesity-related comorbidities. The first approach for obesity management and prevention is the implementation of a diet combined with physical activity. The present review summarizes the compelling evidence showing body composition changes, impact on cardiometabolism and potential adverse effects of very-low calorie, low-and high-carbohydrate, high-protein or low-fat diets. The use of macronutrients during the preprandial and postprandial state has been also reviewed to better understand the metabolic changes induced by different dietary interventions. Conclusion: Dietary changes should be individualised, tailored to food preferences and allow for flexible approaches to reducing calorie intake in order to increase the motivation and compliance of overweight and obese patients.
  • Autores: Álvarez-Cienfuegos Suárez, Francisco Javier (Autor de correspondencia); Rotellar Sastre, Fernando; Valentí Azcarate, Víctor
    Revista: REVISTA ESPAÑOLA DE ENFERMEDADES DIGESTIVAS
    ISSN: 1130-0108 Vol.111 N° 11 2019 págs. 896 - 897
    Resumen
    We have read with great interest the study by Vera MC et al. on the intrasplenic transplantation of hepatocytes from donors receiving the carcinogenic drugs diethylnitrosamine (DEN) and 2-actylaminofluorene (2-AAF). The most important conclusion of the study is that there were no signs of tumor progression in the recipient liver at seven and 60 days after hepatocellular transplantation and no differences were found in the animals with healthy hepatocyte transplants.
  • Autores: Moncada Durruti, Rafael (Autor de correspondencia)
    Revista: ANALES DEL SISTEMA SANITARIO DE NAVARRA
    ISSN: 1137-6627 Vol.42 N° 3 2019 págs. 355 - 356
  • Autores: Unamuno Iñurritegui, Xabier; Portincasa, P.; Fruhbeck Martínez, Gema (Autor de correspondencia)
    Revista: LANCET DIABETES AND ENDOCRINOLOGY
    ISSN: 2213-8587 Vol.7 N° 10 2019 págs. 743 - 745
  • Autores: Salvador Rodríguez, Javier (Autor de correspondencia)
    Revista: ENDOCRINOLOGIA DIABETES Y NUTRICION
    ISSN: 2530-0180 Vol.66 N° 5 2019 págs. 275 - 277
  • Autores: Gargallo Vaamonde, Javier; Perdomo Zelaya, Carolina María; De la Higuera López-Frías, Magdalena; et al.
    Revista: EXPERT OPINION ON PHARMACOTHERAPY
    ISSN: 1465-6566 Vol.20 N° 4 2019 págs. 367 - 371
  • Autores: Hurtado-Pardo, L.; Álvarez-Cienfuegos Suárez, Francisco Javier (Autor de correspondencia); Antoñanzas Pérez, Javier; et al.
    Revista: REVISTA ESPAÑOLA DE ENFERMEDADES DIGESTIVAS
    ISSN: 1130-0108 Vol.111 N° 2 2019 págs. 87 - 93
    Resumen
    Background: the aim of the present study was to analyze the clinicopathological features of patients undergoing pancreatic surgical resections due to cystic neoplasms of the pancreas. Material and methods: demographic data, form of presentation, radiologic images and location of the tumors within the pancreas were analyzed. Data was also collected on the type of surgery (open/laparoscopic), postoperative complications and their severity and oncologic outcomes. Results: eighty-two pancreatic resections were performed. The mean age of patients was 57 years and 49 (59%) were female. Forty-one tumors (50%) were incidental and the most frequent symptoms in the group of symptomatic patients were abdominal pain (63.4%) and weight loss (36.5%). Thirty-two tumors (39%) were located in the tail of the pancreas, 25 (30.5%) in the head and 20 (24.4%) in the body. Thirty-nine (47.5%) distal pancreatectomies, 16 central, ten duodenal pancreatectomies and one enucleation were performed; 40 (48.5%) were carried out laparoscopically. Mean hospital stay was ten days and eight patients (7%) experienced severe complications, one was a pancreatic fistula. Sixty-six tumors (80.5%) were recorded as non-invasive and 16 (19.5%) as invasive: seven intraductal mucinous papillary tumors, one cystic mucinous tumor, four solid pseudopapillary tumors and four cystic neuroendocrine tumors. There was a median follow-up of 64 months; disease-free survival at five and ten years was 97.4% in the patients with non-invasive tumors and 84.6% and 70.5% in the invasive tumors group (p < 0.01). Conclusions: fifty percent of cystic neoplasms of the pancreas are incidental. Two phenotypes exist, invasive and non-invasive.
  • Autores: Ezquerro, S.; Mocha, F.; Fruhbeck Martínez, Gema; et al.
    Revista: JOURNAL OF CLINICAL ENDOCRINOLOGY AND METABOLISM
    ISSN: 0021-972X Vol.104 N° 1 2019 págs. 21 - 37
    Resumen
    CONTEXT: Human obesity is associated with increased circulating TNF-¿, a proinflammatory cytokine that induces hepatocyte cell death. OBJECTIVE: The potential beneficial effects of acylated and desacyl ghrelin in the progression of nonalcoholic fatty liver disease (NAFLD) to nonalcoholic steatohepatitis in obesity via the inhibition of TNF-¿-induced hepatocyte apoptosis, autophagic cell death, and pyroptosis were investigated. DESIGN, SETTINGS, AND PARTICIPANTS: Plasma ghrelin isoforms and TNF-¿ were measured in 158 participants, and hepatocyte cell death was evaluated in liver biopsies from 76 patients with morbid obesity undergoing bariatric surgery with available liver echography and pathology analysis. The effect of acylated and desacyl ghrelin on basal and TNF-¿-induced cell death was determined in vitro in human HepG2 hepatocytes. RESULTS: Circulating TNF-¿ and the acylated/desacyl ghrelin ratio were increased, whereas desacyl ghrelin levels were decreased in patients with obesity and NAFLD. Six months after bariatric surgery, decreased acylated/desacyl ghrelin levels, and improved hepatic function were found. Patients with obesity and type 2 diabetes showed increased hepatic ghrelin O-acyltransferase transcripts as well as an increased hepatic apoptosis, pyroptosis, and compromised autophagy. In HepG2 hepatocytes, acylated and desacyl ghrelin treatment reduced TNF-¿-induced apoptosis, evidenced by lower caspase-8 and caspase-3 cleavage, as well as TUNEL-positive cells and pyroptosis, revealed by decreased caspase-1 activation and lower high-mobility group box 1 expression. Moreover, acylated ghrelin suppressed TNF-¿-activated hepatocyte autophagy, as evidenced by a decreased LC3B-II/I ratio and increased p62 accumulation via AMPK/mTOR. CONCLUSIONS: Ghrelin constitutes a protective factor against hepatocyte cell death. The increased acylated/desacyl ghrelin ratio in patients with obesity and NAFLD might constitute a compensatory mechanism to overcome TNF-¿-induced hepatocyte apoptosis, autophagy, and pyroptosis.
  • Autores: Becerril Mañas, Sara (Autor de correspondencia); Rodríguez Murueta-Goyena, Amaia; Catalán Goñi, Victoria; et al.
    Revista: GENES
    ISSN: 2073-4425 Vol.10 N° 3 2019 págs. 184
    Resumen
    The role of extracellular matrix (ECM) remodeling in fibrosis progression in nonalcoholic fatty liver disease (NAFLD) is complex and dynamic, involving the synthesis and degradation of different ECM components, including tenascin C (TNC). The aim was to analyze the influence of inducible nitric oxide synthase (iNOS) deletion on inflammation and ECM remodeling in the liver of ob/ob mice, since a functional relationship between leptin and iNOS has been described. The expression of molecules involved in inflammation and ECM remodeling was analyzed in the liver of double knockout (DBKO) mice simultaneously lacking the ob and the iNOS genes. Moreover, the effect of leptin was studied in the livers of ob/ob mice and compared to wild-type rodents. Liver inflammation and fibrosis were increased in leptin-deficient mice. As expected, leptin treatment reverted the obesity phenotype. iNOS deletion in ob/ob mice improved insulin sensitivity, inflammation, and fibrogenesis, as evidenced by lower macrophage infiltration and collagen deposition as well as downregulation of the proinflammatory and profibrogenic genes including Tnc. Circulating TNC levels were also decreased. Furthermore, leptin upregulated TNC expression and release via NO-dependent mechanisms in AML12 hepatic cells. iNOS deficiency in ob/ob mice improved liver inflammation and ECM remodeling-related genes, decreasing fibrosis, and metabolic dysfunction. The activation of iNOS by leptin is necessary for the synthesis and secretion of TNC in hepatocytes, suggesting an important role of this alarmin in the development of NAFLD.
  • Autores: Grattagliano, I. ; Montezinho, L. P.; Oliveira, P. J.; et al.
    Revista: BIOCHEMICAL PHARMACOLOGY
    ISSN: 0006-2952 Vol.160 2019 págs. 34 - 45
    Resumen
    Nonalcoholic fatty liver disease (NAFLD) is a condition characterized by the excessive accumulation of triglycerides in hepatocytes. NAFLD is the most frequent chronic liver disease in developed countries, and is often associated with metabolic disorders such as obesity and type 2 diabetes. NAFLD definition encompasses a spectrum of chronic liver abnormalities, ranging from simple steatosis (NAFL), to steatohepatitis (NASH), significant liver fibrosis, cirrhosis, and hepatocellular carcinoma. NAFLD, therefore, represents a global public health issue. Mitochondrial dysfunction occurs in NAFLD, and contributes to the progression to the necro-inflammatory and fibrotic form (NASH). Disrupted mitochondrial function is associated with a decrease in the energy levels and impaired redox balance, and negatively affects cell survival by altering overall metabolism and subcellular trafficking. Such events reduce the tolerance of hepatocytes towards damaging hits, and favour the injurious effects of extra-cellular factors. Here, we discuss the role of mitochondria in NAFLD and focus on potential therapeutic approaches aimed at preserving mitochondrial function.
  • Autores: Fruhbeck Martínez, Gema; Catalán Goñi, Victoria; Rodríguez Murueta-Goyena, Amaia; et al.
    Revista: NUTRIENTS
    ISSN: 2072-6643 Vol.11 N° 2 2019 págs. E454
    Resumen
    Obesity favors the development of cardiometabolic alterations such as type 2 diabetes (T2D) and the metabolic syndrome (MS). Obesity and the MS are distinguished by an increase in circulating leptin concentrations, in parallel to a drop in the levels of adiponectin. Consequently, the Adpn/Lep ratio has been suggested as a maker of dysfunctional adipose tissue. We aimed to investigate in humans (n = 292) the reliability of the Adpn/Lep ratio as a biomarker of adipose tissue dysfunction. We considered that an Adpn/Lep ratio of ¿1.0 can be considered normal, a ratio of ¿0.5 <1.0 suggests moderate-medium increased risk, and a ratio of <0.5 indicates a severe increase in cardiometabolic risk. Using these cut-offs, 5%, 54% and 48% of the lean, normoglycemic and without-MS subjects, respectively, fall within the group with an Adpn/Lep ratio below 0.5; while 89%, 86% and 90% of the obese, with T2D and with MS patients fall within the same group (p < 0.001). A significant negative correlation (r = -0.21, p = 0.005) between the Adpn/Lep ratio and serum amyloid A (SAA) concentrations, a marker of adipose tissue dysfunction, was found. We concluded that the Adpn/Lep ratio is a good indicator of a dysfunctional adipose tissue that may be a useful estimator of obesity- and MS-associated cardiometabolic risk, allowing the identification of a higher number of subjects at risk.
  • Autores: Anon-Hidalgo, J.; Catalán Goñi, Victoria; Rodríguez Murueta-Goyena, Amaia; et al.
    Revista: AGING-US
    ISSN: 1945-4589 Vol.11 N° 6 2019 págs. 1733 - 1744
    Resumen
    Growth differentiation factor 11 (GDF11) is a member of the transforming growth factor beta (TGF beta) superfamily which declines with age and exerts anti-aging regenerative effects in skeletal muscle in mice. However, recent data in humans and mice are conflicting casting doubts about its true functional actions. The aim of the present study was to compare the circulating concentrations of GDF11 in individuals of different ages as well as body weight and glycemic status. Serum concentrations of GDF11 were measured by ELISA in 319 subjects. There was a significant increase in GDF11 concentrations in people in the 41-50 y group and a decline in the elder groups (61-70 and 71-80 y groups, P=0.008 for the comparison between all age groups). However, no significant correlation between fat-free mass index (FFMI), a formula used to estimate the amount of muscle mass in relation to height, and IogGDF11 was observed (r=0.08, P=0.197). Moreover, no significant differences in circulating concentrations of GDF11 regarding obesity or glycemic status were found. Serum GDF11 concentrations in humans decrease in older ages being unaltered in obesity and T2D. Further studies should determine the exact pathophysiological role of GDF11 in aging.
  • Autores: Unamuno Iñurritegui, Xabier; Izaguirre Ascargorta, Maitane; Gómez Ambrosi, Javier; et al.
    Revista: NUTRIENTS
    ISSN: 2072-6643 Vol.11 N° 9 2019 págs. 2069
    Resumen
    Bariatric surgery remains the most effective option for achieving important and sustained weight loss. We explored the effects of Roux-en-Y gastric bypass (RYGB) on the circulating levels of adiponectin, leptin, and the adiponectin/leptin (Adpn/Lep) ratio in patients with obesity and type 2 diabetes (T2D). Twenty-five T2D volunteers undergoing RYGB were included in the study, and further subclassified as patients that responded or not to RYBG, regarding remission of T2D. Anthropometric and biochemical variables were evaluated before and after RYGB. Obese patients with T2D exhibited an increase (p < 0.0001) in the Adpn/Lep ratio after RYGB. Changes in the Adpn/Lep ratio correlated better with changes in anthropometric data (p < 0.001) than with the variations of adiponectin or leptin alone. Multiple regression analysis revealed that the change in the Adpn/Lep ratio in patients with T2D was an independent predictor of the changes in body mass index (p < 0.001) and body fat percentage (p = 0.022). However, the Adpn/Lep ratio did not differ between individuals with or without T2D remission after RYGB. In summary, the current study demonstrated that after weight and body fat loss following RYGB, the Adpn/Lep ratio increased in patients with obesity and T2D.
  • Autores: Lara, J. P. (Autor de correspondencia); Compan, A.; Vargas-Nunez, J. A.; et al.
    Revista: REVISTA CLINICA ESPAÑOLA
    ISSN: 0014-2565 Vol.219 N° 2 2019 págs. 84 - 89
    Resumen
    The significant and progressive reduction in the number of permanent teachers in medical schools (professor, associate professor and assistant professor) is a reason for concern for the National Conference of Deans. This reduction will intensify in the coming decade (2017-2026). Forty-three percent of the permanent faculty will retire, as will 55% of the faculty linked to clinical areas, 34% of the faculty not linked to clinical areas and 32% of the faculty of basic areas. This deficit is significant now, and, in a few years, the situation wilt be unsustainable, especially in the clinical areas. This report reveals the pressing need to adopt urgent measures to alleviate the present situation and prevent a greater problem. The training of future physicians, immediately responsible for the health of our society, depends largely on the theoretical and practical training taught in medical schools, with the essential collaboration of healthcare institutions. Paradoxically, while the number of teachers decreases substantially, there is an exponential increase in the number of medical schools and students who are admitted every year without academic or healthcare justification.
  • Autores: Izaguirre Ascargorta, Maitane; Gómez Ambrosi, Javier; Rodríguez Murueta-Goyena, Amaia; et al.
    Revista: JOURNAL OF CLINICAL MEDICINE
    ISSN: 2077-0383 Vol.8 N° 4 2019 págs. 479
    Resumen
    Objective: Glucagon-like peptide (GLP)-1 has been proposed as a key candidate in glucose improvements after bariatric surgery. Our aim was to explore the role of GLP-1 in surgically-induced type 2 diabetes (T2D) improvement and its capacity to regulate human adipocyte inflammation. Methods: Basal circulating concentrations of GLP-1 as well as during an oral glucose tolerance test (OGTT) were measured in lean and obese volunteers with and without T2D (n = 93). In addition, GLP-1 levels were determined before and after weight loss achieved by Roux-en-Y gastric bypass (RYGB) (n = 77). The impact of GLP-1 on inflammation signalling pathways was also evaluated. Results: We show that the reduced (p < 0.05) circulating levels of GLP-1 in obese T2D patients increased (p < 0.05) after RYGB. The area under the curve was significantly lower in obese patients with (p < 0.01) and without (p < 0.05) T2D compared to lean volunteers while obese patients with T2D exhibited decreased GLP-1 levels at baseline (p < 0.05) and 120 min (p < 0.01) after the OGTT. Importantly, higher (p < 0.05) pre-operative GLP-1 concentrations were found in patients with T2D remission after RYGB. We also revealed that exendin-4, a GLP-1 agonist, downregulated the expression of inflammation-related genes (IL1B, IL6, IL8, TNF) and, conversely, upregulated the mRNA levels of ADIPOQ in human visceral adipocytes. Furthermore, exendin-4 blocked (p < 0.05) LPS-induced inflammation in human adipocytes via downregulating the expression and secretion of key inflammatory markers. Conclusions: Our data indicate that GLP-1 may contribute to glycemic control and exert a role in T2D remission after RYGB. GLP-1 is also involved in limiting inflammation in human visceral adipocytes.
  • Autores: Fruhbeck Martínez, Gema (Autor de correspondencia); Busetto, L.; Dicker, D. ; et al.
    Revista: OBESITY FACTS
    ISSN: 1662-4025 Vol.12 N° 2 2019 págs. 131 - 136
    Resumen
    Obesity is a frequent, serious, complex, relapsing, and chronic disease process that represents a major public health problem. The coining of obesity as an adiposity-based chronic disease (ABCD) is of particular relevance being in line with EASO's proposal to improve the International Classification of Diseases ICD-11 diagnostic criteria for obesity based on three dimensions, namely etiology, degree of adiposity, and health risks. The body mass index as a unique measurement of obesity does not reflect the whole complexity of the disease. Obesity complications are mainly determined by 2 pathological processes, i.e., physical forces (fat mass disease) as well as endocrine and immune responses (sick fat disease), which are embedded in a cultural and physical context leading to a specific ABCD stage. (c) 2019 The Author(s) Published by S. Karger AG, Basel
  • Autores: Reyes-Garcia, R. (Autor de correspondencia); Moreno-Perez, O. ; Tejera-Perez, C. ; et al.
    Revista: ENDOCRINOLOGIA DIABETES Y NUTRICION
    ISSN: 2530-0180 Vol.66 N° 7 2019 págs. 443 - 458
    Resumen
    Objective: Treatment of type 2 diabetes mellitus (T2DM) is complex and is intended to decrease morbidity and mortality. Management should therefore include adequate diabetes education, lifestyle changes, drug treatment to achieve early blood glucose control and reduction of cardiovascular (CV) risk factors, early detection and treatment of complications, and assessment of associated comorbidities. The objective was to prepare a document including all aspects required for a comprehensive approach to T2DM. Participants: Members of the Diabetes Mellitus Working Group of the Spanish Society of Endo-crinology. Methods: The available evidence regarding each aspect of diabetes management (blood glucose control goals, diet and exercise, drug treatment, risk factor management and control, detection of complications, and management of frail patients) was reviewed. Recommendations were formulated based on the grades of evidence stated in the 2018 Standards of Medical Care in Diabetes. Recommendations were discussed and agreed by the working group members. Conclusions: This document is intended to provide evidence-based practical recommendations for comprehensive management of T2DM by clinical endocrinologists.
  • Autores: Steward, T. ; Mestre-Bach, G.; Granero, R. ; et al.
    Revista: SCIENTIFIC REPORTS
    ISSN: 2045-2322 Vol.9 N° 1 2019 págs. 7910
    Resumen
    Orexins/hypocretins are neuropeptides implicated in numerous processes, including food intake and cognition. The role of these peptides in the psychopathology of anorexia nervosa (AN) remains poorly understood. The aim of the current study was to evaluate the associations between plasma orexin-A (OXA) concentrations and neuropsychological functioning in adult women with AN, and a matched control group. Fasting plasma OXA concentrations were taken in 51 females with AN and in 51 matched healthy controls. Set-shifting was assessed using the Wisconsin Card Sorting Test (WCST), whereas decision making was measured using the Iowa Gambling Task (IGT). The AN group exhibited lower plasma OXA levels than the HC group. Lower mean scores were obtained on the IGT in AN patients. WCST perseverative errors were significantly higher in the AN group compared to HC. In both the AN and HC group, OXA levels were negatively correlated with WCST non-perseverative errors. Reduced plasma OXA concentrations were found to be associated with set-shifting impairments in AN. Taking into consideration the function of orexins in promoting arousal and cognitive flexibility, future studies should explore whether orexin partly underpins the cognitive impairments found in AN.
  • Autores: Caterson, I. D. (Autor de correspondencia); Alfadda, A. A.; Auerbach, P. ; et al.
    Revista: DIABETES OBESITY AND METABOLISM
    ISSN: 1462-8902 Vol.21 N° 8 2019 págs. 1914 - 1924
    Resumen
    Aims Despite increased recognition as a chronic disease, obesity remains greatly underdiagnosed and undertreated. We aimed to identify international perceptions, attitudes, behaviours and barriers to effective obesity care in people with obesity (PwO) and healthcare professionals (HCPs). Materials and methods An online survey was conducted in 11 countries. Participants were adults with obesity and HCPs who were primarily concerned with direct patient care. Results A total of 14 502 PwO and 2785 HCPs completed the survey. Most PwO (68%) and HCPs (88%) agreed that obesity is a disease. However, 81% of PwO assumed complete responsibility for their own weight loss and only 44% of HCPs agreed that genetics were a barrier. There was a median of three (mean, six) years between the time PwO began struggling with excess weight or obesity and when they first discussed their weight with an HCP. Many PwO were concerned about the impact of excess weight on health (46%) and were motivated to lose weight (48%). Most PwO (68%) would like their HCP to initiate a conversation about weight and only 3% were offended by such a conversation. Among HCPs, belief that patients have little interest in or motivation for weight management may constitute a barrier for weight management conversations. When discussed, HCPs typically recommended lifestyle changes; however, more referrals and follow-up appointments are required. Conclusions Our international dataset reveals a need to increase understanding of obesity and improve education concerning its physiological basis and clinical management. Realization that PwO are motivated to lose weight offers an opportunity for HCPs to initiate earlier weight management conversations.
  • Autores: Folgueira, C.; Beiroa, D.; Porteiro, B. ; et al.
    Revista: NATURE METABOLISM
    ISSN: 2522-5812 Vol.1 N° 8 2019 págs. 811 - 829
    Resumen
    Dopamine signalling is a crucial part of the brain reward system and can affect feeding behaviour. Dopamine receptors are also expressed in the hypothalamus, which is known to control energy metabolism in peripheral tissues. Here we show that pharmacological or chemogenetic stimulation of dopamine receptor 2 (D2R) expressing cells in the lateral hypothalamic area (LHA) and the zona incerta (ZI) decreases body weight and stimulates brown fat activity in rodents in a feeding-independent manner. LHA/ZI D2R stimulation requires an intact sympathetic nervous system and orexin system to exert its action and involves inhibition of PI3K in the LHA/ZI. We further demonstrate that, as early as 3 months after the onset of treatment, patients treated with the D2R agonist cabergoline experience an increase in energy expenditure that persists for one year, leading to total body weight and fat loss through a prolactin-independent mechanism. Our results may provide a mechanistic explanation for how clinically used D2R agonists act in the central nervous system to regulate energy balance.
  • Autores: Ortega, F. J. (Autor de correspondencia); Moreno-Navarrete, J. M.; Mercader, J. M.; et al.
    Revista: FASEB JOURNAL
    ISSN: 0892-6638 Vol.33 N° 8 2019 págs. 9656 - 9671
    Resumen
    During adipogenesis, preadipocytes' cytoskeleton reorganizes in parallel with lipid accumulation. Failure to do so may impact the ability of adipose tissue (AT) to shift between lipid storage and mobilization. Here, we identify cytoskeletal transgelin 2 (TAGLN2) as a protein expressed in AT and associated with obesity and inflammation, being normalized upon weight loss. TAGLN2 was primarily found in the adipose stromovascular cell fraction, but inflammation, TGF-beta, and estradiol also prompted increased expression in human adipocytes. Tagln2 knockdown revealed a key functional role, being required for proliferation and differentiation of fat cells, whereas transgenic mice overexpressing Tagln2 using the adipocyte protein 2 promoter disclosed remarkable sex-dependent variations, in which females displayed healthy obesity and hypertrophied adipocytes but preserved insulin sensitivity, and males exhibited physiologic changes suggestive of defective AT expandability, including increased number of small adipocytes, activation of immune cells, mitochondrial dysfunction, and impaired metabolism together with decreased insulin sensitivity. The metabolic relevance and sexual dimorphism of TAGLN2 was also outlined by genetic variants that may modulate its expression and are associated with obesity and the risk of ischemic heart disease in men. Collectively, current findings highlight the contribution of cytoskeletal TAGLN2 to the obese phenotype in a gender-dependent manner.-Ortega, F. J., Moreno-Navarrete, J. M., Mercader, J. M., Gomez-Serrano, M., Garcia-Santos, E., Latorre, J., Lluch, A., Sabater, M., Caballano-Infantes, E., Guzman, R., Macias-Gonzalez, M., Buxo, M., Girones, J., Vilallonga, R., Naon, D., Botas, P., Delgado, E., Corella, D., Burcelin, R., Fruhbeck, G., Ricart, W., Simo, R., Castrillon-Rodriguez, I., Tinahones, F. J., Bosch, F., Vidal-Puig, A., Malagon, M. M., Peral, B., Zorzano, A., Fernandez-Real, J. M. Cytoskeletal transgelin 2 contributes to gender-dependent adipose tissue expandability and immune function.
  • Autores: Sanchez, M. ; Sanchez, E.; Hernandez, M.; et al.
    Revista: NUTRIENTS
    ISSN: 2072-6643 Vol.11 N° 6 2019 págs. 1359
    Resumen
    There is a close relationship between lifestyle behaviors and excess adiposity. Although body mass index (BMI) is the most used approach to estimate excess weight, other anthropometric indices have been developed to measure total body and abdominal adiposity. However, little is known about the impact of physical activity and adherence to a Mediterranean diet on these indices. Here we report the results of a cross-sectional study with 6672 middle-aged subjects with low to moderate cardiovascular risk from the Ilerda Vascular (ILERVAS) project. The participants' adherence to physical activity (International Physical Activity Questionnaire short form) and MedDiet (Mediterranean Diet Adherence Screener) was evaluated. Measures of total adiposity (BMI, Clinica Universidad de Navarra-Body Adiposity Estimator (CUN-BAE), and Deurenberg's formula), central adiposity (waist and neck circumferences, conicity index, waist to height ratio, Bonora's equation, A body adiposity index, and body roundness index), and lean body mass (Hume formula) were assessed. Irrespective of sex, lower indices of physical activity were associated with higher values of total body fat and central adiposity. This result was constant regardless of the indices used to estimate adiposity. However, the association between MedDiet and obesity indices was much less marked and more dependent on sex than that observed for physical activity. Lean body mass was influenced by neither physical activity nor MedDiet adherence. No joint effect between physical activity and MedDiet to lower estimated total or central adiposity indices was shown. In conclusion, physical activity is related to lower obesity indices in a large cohort of middle-aged subjects. MedDiet showed a slight impact on estimated anthropometric indices, with no joint effect when considering both lifestyle variables. ClinTrials.gov Identifier: NCT03228459.
  • Autores: Christou, G. A. ; Katsiki, N.; Blundell, J. ; et al.
    Revista: OBESITY REVIEWS
    ISSN: 1467-7881 Vol.20 N° 6 2019 págs. 805 - 815
    Resumen
    Semaglutide is a glucagon-like peptide-1 receptor agonist (GLP-1 RA) with a long elimination half-life, allowing subcutaneous (sc) administration once per week. Both the European Medicines Agency (EMA) and the Food and Drug Administration (FDA) recently approved once-weekly sc semaglutide for the treatment of type 2 diabetes mellitus (T2DM). The weight loss efficacy of once-weekly sc semaglutide appears to be superior compared with the other once-weekly GLP-1 RAs in patients with T2DM. Semaglutide was recently evaluated as an antiobesity drug in a phase II dose-finding trial, which demonstrated superior weight loss efficacy of once daily sc semaglutide compared with both placebo and once daily 3.0 mg liraglutide in patients with obesity but without T2DM. The magnitude of semaglutide-induced weight loss in this study exceeded the criteria of both the EMA and FDA for antiobesity drugs, and there were no safety concerns, indicating the eligibility of once daily sc semaglutide as a future antiobesity drug.
  • Autores: Pérez Pevida, Belén (Autor de correspondencia); Núñez Córdoba, Jorge María; Romero, S.; et al.
    Revista: JOURNAL OF TRANSLATIONAL MEDICINE
    ISSN: 1479-5876 Vol.17 2019 págs. 48
    Resumen
    Background and aims: Obesity is associated with impaired glucose tolerance which is a risk factor for cardiovascular risk. However, the oral glucose tolerance test (OGTT) is not usually performed in patients with normal fasting glycaemia, thus offering false reassurance to patients with overweight or obesity who may have post-prandial hyperglycaemia. As an alternative to resource demanding OGTTs, we aimed to examine the predictive value of anthropometric measures of total and central fat distribution for post-prandial hyperglycaemia in patients with overweight and obesity with normal fasting glycaemia enrolled in the DICAMANO study. Methods: We studied 447 subjects with overweight/obesity with a fasting glucose value <= 5.5 mmol l(-1) (99 mg dl(-1)) and BMI >= 25 kg/m(2) who underwent a 75-g OGTT. Post-prandial hyperglycaemia was defined as a glucose level >= 7.8 mmol l(-1) (140 mg dl(-1)) 2-h after the OGTT. The anthropometric measurements included body mass index, body adiposity index, waist circumference, neck circumference, waist-to-hip ratio and waist-to-height ratio. Results: The prevalence of post-prandial hyperglycaemia was 26%. Mean 1-h OGTT glucose levels, insulin resistance and beta cell dysfunction was higher in those subjects in the highest tertile for each anthropometric measurement, irrespective of fasting glucose level. Central fat depot anthropometric measurements were strongly and independently associated with an increased risk of post-prandial hyperglycaemia. After multivariable-adjustment for fasting plasma glucose level, smoking, and physical activity level, the odds ratio (95% confidence intervals) for the presence of post-prandial hyperglycaemia for neck circumference, waist circumference and waist-to-height ratio were 3.3 (1.4, 7.7), 2.4 (1.4, 4.4) and 2.5 (1.4, 4.5), respectively. Conclusions: In this large and comprehensively phenotyped cohort, one in four subjects had post-prandial hyperglycaemia despite normal fasting glycaemia. Anthropometric indices of central fat distribution were strongly and independently associated with an increased risk of post-prandial hyperglycaemia. These results support the association between central adiposity and glucose derangements and demonstrate the clinical usefulness of anthropometric measurements as screening tools for the selection of patients who are most likely to benefit from an OGTT.
  • Autores: Ceperuelo-Mallafre, V.; Llaurado, G. ; Keiran, N. ; et al.
    Revista: DIABETES CARE
    ISSN: 0149-5992 Vol.42 N° 10 2019 págs. 1956 - 1965
    Resumen
    OBJECTIVE To determine the potential use of baseline circulating succinate to predict type 2 diabetes remission after bariatric surgery. RESEARCH DESIGN AND METHODS Forty-five obese patients with diabetes were randomly assigned to Roux-en-Y gastric bypass (RYGB), sleeve gastrectomy (SG), or laparoscopic greater curvature plication. Anthropometric parameters were evaluated, and a complete biochemical analysis including circulating serum succinate concentrations was performed at baseline and 1 year after surgery. The results were externally validated in a second cohort including 88 obese patients with diabetes assigned to RYGB or SG based on clinical criteria. RESULTS Succinate baseline concentrations were an independent predictor of diabetes remission after bariatric surgery. Patients achieving remission after 1 year had lower levels of baseline succinate (47.8 [37.6-64.6] mu mol/L vs. 64.1 [52.5-82.9] mu mol/L; P = 0.018). Moreover, succinate concentrations were significantly decreased 1 year after surgery (58.9 [46.4-82.4] mu mol/L vs. 46.0 [35.8-65.3] mu mol/L, P = 0.005). In multivariate analysis, the best logistic regression model showed that baseline succinate (odds ratio [OR] 11.3, P = 0.031) and the type of surgery (OR 26.4, P = 0.010) were independently associated with remission. The C-statistic for this model was 0.899 (95% CI 0.809-0.989) in the derivation cohort, which significantly improved the prediction of remission compared with current available scores, and 0.729 (95% CI 0.612-0.846) in the validation cohort. Interestingly, patients had a different response to the type of surgery according to baseline succinate, with significant differences in remission rates. CONCLUSIONS Circulating succinate is reduced after bariatric surgery. Baseline succinate levels have predictive value for diabetes remission independently of previously described presurgical factors and improve upon the current available scores to predict remission.
  • Autores: Morillas, C. (Autor de correspondencia); Escalada San Martín, Francisco Javier; Palomares, R.; et al.
    Revista: DIABETES THERAPY
    ISSN: 1869-6953 Vol.10 N° 5 2019 págs. 1893 - 1907
    Resumen
    Introduction The aim of this Delphi study is to unveil the management of patients with type 2 diabetes (T2D) and different levels of complexity in the clinical practice in Spain. Methods Based on the common management practices of T2D profiles reported by Spanish endocrinologists, a Delphi questionnaire of 55 statements was developed and responded to by a national panel (n = 101). Results A consensus was reached for 30 of the 55 statements. Regarding overweight patients inadequately controlled with metformin, treatment with a sodium-glucose transport protein 2 inhibitor (SGLT2-I) is preferred over treatment with a dipeptidyl peptidase-4 inhibitor (DPP4-I). If the patient is already being treated with a DPP4-I, an SGLT2-I is added on to the treatment regimen rather than replacing the DPP4-I. Conversely, if the treatment regimen includes a sulfonylurea, it is usually replaced by other antihyperglycemic agents. Current treatment trends in uncontrolled obese patients include the addition of an SGLT2-I or a glucagon-like peptide-1 receptor agonist (GLP1-RA) to background therapy. When the glycated hemoglobin target is not reached, triple therapy with metformin + GLP1-RA + SGLT2-I is initiated. Although SGLT2-Is are the treatment of choice in patients with T2D and heart failure or uncontrolled hypertension, no consensus was reached regarding the preferential use of SGLT2-Is or GLP1-RAs in patients with established cardiovascular disease. Conclusion Consensus has been reached for a variety of statements regarding the management of several T2D profiles. Achieving a more homogeneous management of complex patients with T2D may require further evidence and a better understanding of the key drivers for treatment choice. Funding Logistic support was provided by ESTEVE Pharmaceuticals S.A Spain.
  • Autores: Martinaitis, L.; Tuero Ojanguren, Carlota; Landecho Acha, Manuel Fortún; et al.
    Revista: REVISTA ESPAÑOLA DE ENFERMEDADES DIGESTIVAS
    ISSN: 1130-0108 Vol.111 N° 5 2019 págs. 371 - 377
    Resumen
    Purpose: to assess the long-term benefits of bariatric surgery in super-obese (body mass index [BMI] = 50) and in elderly obese (age > 60 years) populations. Methods: one hundred and twenty one patients who underwent laparoscopic Roux-en-Y gastric bypass or laparoscopic sleeve gastrectomy in a university hospital were retrospectively subdivided into the following groups: BMI < 50 vs = 50 and age < 60 vs = 60 years. Weight loss, body composition and comorbidity outcomes were registered after one and six months and one, two, three and five years with 100%, 93%, 89%, 80%, 75% and 60% successful follow-up. Results: the percentage of excess BMI loss (% EBMIL) was comparable between BMI groups and age groups and the difference in the long-term follow up was not statistically significant (p > 0.05). Complication rates, comorbidity resolution, reduction in body fat and increase in fat-free mass were comparable between BMI groups and age groups. Gastric bypass resulted in a greater weight loss compared to sleeve gastrectomy. The % EBMIL was 65.2% vs 46.7% (p = 0.002), 65.8% vs 44.9% (p = 0.004), 64.4% vs 30.5% (p = 0.001), 55.6% vs 17.6% (p = 0.016) at one, two, three and five years postoperative, respectively. Similarly, in the super-obese group, weight loss was more pronounced after gastric bypass versus sleeve gastrectomy. Conclusions: bariatric surgery in super-obese and elderly populations is an effective and safe weight loss measure with a good comorbidity resolution in the long-term. Gastric bypass is superior to sleeve gastrectomy in terms of long-term weight loss and comorbidity resolution in all the groups investigated.
  • Autores: Anon-Hidalgo, J.; Catalán Goñi, Victoria; Rodríguez Murueta-Goyena, Amaia; et al.
    Revista: JOURNAL OF CLINICAL MEDICINE
    ISSN: 2077-0383 Vol.8 N° 6 2019 págs. 878
    Resumen
    Growth differentiation factor 11 (GDF11) is a member of the transforming growth factor (TGF)-beta superfamily which declines with age and has been proposed as an anti-aging factor with regenerative effects in skeletal muscle in mice. However, recent data in humans and mice are conflicting, casting doubts about its true functional actions. The aim of the present study was to analyze the potential involvement of GFD11 in energy homeostasis in particular in relation with thyroid hormones. Serum concentrations of GDF11 were measured by enzyme-linked immunosorbent assay (ELISA) in 287 subjects. A highly significant positive correlation was found between GDF11 and thyroid-stimulating hormone (TSH) concentrations (r = 0.40, p < 0.001). Neither resting energy expenditure (REE) nor REE per unit of fat-free mass (REE/FFM) were significantly correlated (p > 0.05 for both) with GDF11 levels. In a multiple linear regression analysis, the model that best predicted logGDF11 included logTSH, leptin, body mass index (BMI), age, and C-reactive protein (logCRP). This model explained 37% of the total variability of logGDF11 concentrations (p < 0.001), with only logTSH being a significant predictor of logGDF11. After segregating subjects by TSH levels, those within the low TSH group exhibited significantly decreased (p < 0.05) GDF11 concentrations as compared to the normal TSH group or the high TSH group. A significant correlation of GDF11 levels with logCRP (r = 0.19, p = 0.025) was found. GDF11 levels were not related to the presence of hypertension or cardiopathy. In conclusion, our results show that circulating concentrations of GDF11 are closely associated with TSH concentrations and reduced in subjects with low TSH levels. However, GDF11 is not related to the regulation of energy expenditure. Our data also suggest that GDF11 may be involved in the regulation of inflammation, without relation to cardiac function. Further research is needed to elucidate the role of GDF11 in metabolism and its potential involvement in thyroid pathophysiology.
  • Autores: Ezquerro, S. ; Mendez-Gimenez, L.; Becerril Mañas, Sara; et al.
    Revista: EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
    ISSN: 0014-2972 Vol.49 N° Supl. 1 2019 págs. 55 - 56
  • Autores: Ezquerro, S. ; Mocha, F.; Fruhbeck Martínez, Gema; et al.
    Revista: EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
    ISSN: 0014-2972 Vol.49 N° Supl. 1 2019 págs. 79 - 80
  • Autores: Catalán Goñi, Victoria; Gómez Ambrosi, Javier; Rodríguez Murueta-Goyena, Amaia; et al.
    Revista: EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
    ISSN: 0014-2972 Vol.49 N° Supl. 1 2019 págs. 150
  • Autores: Lujan Colas, Juan; Tuero Ojanguren, Carlota; Moncada Durruti, Rafael; et al.
    Revista: OBESITY SURGERY
    ISSN: 0960-8923 Vol.29 N° Suppl.5 2019 págs. 302 - 302
  • Autores: Gómez Ambrosi, Javier; González Crespo, Ignacio; Catalán Goñi, Victoria; et al.
    Revista: EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
    ISSN: 0014-2972 Vol.49 N° Supl. 1 2019 págs. 147 - 147
  • Autores: Becerril Mañas, Sara; Rodríguez Murueta-Goyena, Amaia; Catalán Goñi, Victoria; et al.
    Revista: EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
    ISSN: 0014-2972 Vol.49 N° Supl. 1 2019 págs. 148 - 149
  • Autores: Valentí Azcarate, Víctor; Tuero Ojanguren, Carlota; Moncada Durruti, Rafael; et al.
    Revista: OBESITY SURGERY
    ISSN: 0960-8923 Vol.29 N° Supl. 5 2019 págs. 727 - 727
  • Autores: Fruhbeck Martínez, Gema (Autor de correspondencia)
    Revista: EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
    ISSN: 0014-2972 Vol.49 N° Supl. 1 2019 págs. 35 - 35
  • Autores: Ahechu Garayoa, Patricia; Zozaya Larequi, Gabriel Nicolás; Martí Cruchaga, Pablo; et al.
    Revista: FRONTIERS IN IMMUNOLOGY
    ISSN: 1664-3224 Vol.9 2018 págs. 2918
    Resumen
    Emerging evidence reveals that adipose tissue-associated inflammation is a main mechanism whereby obesity promotes colorectal cancer risk and progression. Increased inflammasome activity in adipose tissue has been proposed as an important mediator of obesity-induced inflammation and insulin resistance development. Chronic inflammation in tumor microenvironments has a great impact on tumor development and immunity, representing a key factor in the response to therapy. In this context, the inflammasomes, main components of the innate immune system, play an important role in cancer development showing tumor promoting or tumor suppressive actions depending on the type of tumor, the specific inflammasome involved, and the downstream effector molecules. The inflammasomes are large multiprotein complexes with the capacity to regulate the activation of caspase-1. In turn, caspase-1 enhances the proteolytic cleavage and the secretion of the inflammatory cytokines interleukin (IL)-1 beta and IL-18, leading to infiltration of more immune cells and resulting in the generation and maintenance of an inflammatory microenvironment surrounding cancer cells. The inflammasomes also regulate pyroptosis, a rapid and inflammation-associated form of cell death. Recent studies indicate that the inflammasomes can be activated by fatty acids and high glucose levels linking metabolic danger signals to the activation of inflammation and cancer development. These data suggest that activation of the inflammasomes may represent a crucial step in the obesity-associated cancer development. This review will also focus on the potential of inflammasome-activated pathways to develop new therapeutic strategies for the prevention and treatment of obesity-associated colorectal cancer development.
  • Autores: Vecchie, A.; Dallegri, F. ; Carbone, F.; et al.
    Revista: EUROPEAN JOURNAL OF INTERNAL MEDICINE
    ISSN: 0953-6205 Vol.48 2018 págs. 6 - 17
    Resumen
    The pro-inflammatory state of the visceral adipose tissue (VAT) is supposed to accelerate cardiovascular (CV) and metabolic diseases in obese subjects. Some studies have recently reported an improved CV prognosis in certain obese and overweight patients as compared with leaner ones. This phenomenon, known as the "obesity paradox" (OP), has been described in many chronic diseases. This narrative review is based on the material searched for and obtained via PubMed and Web of Science up to May 2017. The search terms we used were: "obesity, paradox, adipose tissue" in combination with "cardiovascular, coronary heart disease, heart failure, arrhythmias". Using the current Body Mass Index (BMI)-based obesity definition, individuals with different clinical and biochemical characteristics are gathered together in the same category. Emerging evidence point to the existence of many "Obesity phenotypes" with different association with CV risk, accordingly to physical and life-style features. In this narrative review, we discussed if obesity phenotypes may be associated with a different CV risk, potentially explaining the OP. As a globally accepted definition of obesity is still lacking, we emphasized the need of a new approach, which should consider the heterogeneity of obesity. Better defining "obesities" and related CV risk is critical to markedly improve the classical BMI-based definition of obesity.
  • Autores: Pedro-Botet, J. (Autor de correspondencia); Ascaso, J. F.; Barrios, V. ; et al.
    Revista: DIABETES, METABOLIC SYNDROME AND OBESITY
    ISSN: 1178-7007 Vol.11 2018 págs. 683 - 697
    Resumen
    Metabolic syndrome (MetS), a disorder with a high and growing prevalence, is a recognized risk factor for cardiovascular disease (CVD) and type 2 diabetes. It is a constellation of clinical and metabolic risk factors that include abdominal obesity, dyslipidemia, glucose intolerance, and hypertension. Unfortunately, MetS is typically underrecognized, and there is great heterogeneity in its management, which can hamper clinical decision-making and be a barrier to achieving the therapeutic goals of CVD and diabetes prevention. Although no single treatment for MetS as a whole currently exists, management should be targeted at treating the conditions contributing to it and possibly reversing the risk factors. All this justifies the need to develop recommendations that adapt existing knowledge to clinical practice in our healthcare system. In this regard, professionals from different scientific societies who are involved in the management of the different MetS components reviewed the available scientific evidence focused basically on therapeutic aspects of MetS and developed a consensus document to establish recommendations on therapeutic goals that facilitate their homogenization in clinical decision-making.
  • Autores: Mendez-Gimenez, L.; Ezquerro, S.; da Silva, I. V. ; et al.
    Revista: FRONTIERS IN CHEMISTRY
    ISSN: 2296-2646 Vol.6 2018 págs. 99
    Resumen
    Aquaporins comprise a family of 13 members of water channels (AQP0-12) that facilitate a rapid transport of water across cell membranes. In some cases, these pores are also permeated by small solutes, particularly glycerol, urea or nitric oxide, among other solutes. Several aquaporins have been identified in the pancreas, an exocrine and endocrine organ that plays an essential role in the onset of insulin resistance and type 2 diabetes. The exocrine pancreas, which accounts for 90% of the total pancreas, secretes daily large volumes of a near-isotonic fluid containing digestive enzymes into the duodenum. AQP1, AQP5, and AQP8 contribute to fluid secretion especially from ductal cells, whereas AQP12 allows the proper maturation and exocytosis of secretory granules in acinar cells of the exocrine pancreas. The endocrine pancreas (10% of the total pancreatic cells) is composed by the islets of Langerhans, which are distributed in alpha, beta, delta, epsilon, and pancreatic polypeptide (PP) cells that secrete glucagon, insulin, somatostatin, ghrelin and PP, respectively. AQP7, an aquaglyceroporin permeated by water and glycerol, is expressed in pancreatic beta-cells and murine studies have confirmed its participation in insulin secretion, triacylglycerol synthesis and proliferation of these endocrine cells. In this regard, transgenic AQP7-knockout mice develop adult-onset obesity, hyperinsulinemia, increased intracellular triacylglycerol content and reduced beta-cell mass in Langerhans islets. Moreover, we have recently reported that AQP7 upregulation in beta-cells after bariatric surgery, an effective weight loss surgical procedure, contributes, in part, to the improvement of pancreatic steatosis and insulin secretion through the increase of intracytoplasmic glycerol in obese rats. Human studies remain scarce and controversial, with some rare cases of loss-of function mutations of the AQP7 gene being associated with the onset of type 2 diabetes. The present Review is focused on the role of aquaporins in the physiology and pathophysiology of the pancreas, highlighting the role of pancreatic AQP7 as a novel player in the control of b-cell function and a potential anti-diabetic-drug.
  • Autores: Unamuno, X.; Gómez Ambrosi, Javier; Rodríguez Murueta-Goyena, Amaia; et al.
    Revista: EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
    ISSN: 0014-2972 Vol.48 N° 9 2018 págs. e12997
    Resumen
    Obesity, a worldwide epidemic, confers increased risk for multiple serious conditions, including type 2 diabetes, cardiovascular diseases, nonalcoholic fatty liver disease and cancer. Adipose tissue is considered one of the largest endocrine organs in the body as well as an active tissue for cellular reactions and metabolic homeostasis rather than an inert tissue for energy storage. The functional pleiotropism of adipose tissue relies on its ability to synthesize and release a large number of hormones, cytokines, extracellular matrix proteins and growth and vasoactive factors, collectively termed adipokines that influence a variety of physiological and pathophysiological processes. In the obese state, excessive visceral fat accumulation causes adipose tissue dysfunctionality that strongly contributes to the onset of obesity-related comorbidities. The mechanisms underlying adipose tissue dysfunction include adipocyte hypertrophy and hyperplasia, increased inflammation, impaired extracellular matrix remodelling and fibrosis together with an altered secretion of adipokines. This review describes how adipose tissue becomes inflamed in obesity and summarizes key players and molecular mechanisms involved in adipose inflammation.
  • Autores: Catalán Goñi, Victoria (Autor de correspondencia); Salvador Rodríguez, Javier; Fruhbeck Martínez, Gema; et al.
    Revista: ANALES DEL SISTEMA SANITARIO DE NAVARRA
    ISSN: 1137-6627 Vol.41 N° 2 2018 págs. 287 - 289
  • Autores: Landecho Acha, Manuel Fortún; Inigo-Morras, E.; Valentí Azcarate, Víctor (Autor de correspondencia)
    Revista: OBESITY SURGERY
    ISSN: 0960-8923 Vol.28 N° 10 2018 págs. 3299 - 3300
  • Autores: Silva Frojan, Camilo (Autor de correspondencia); Llavero Valero, María; Varo Cenarruzabeitia, Nerea; et al.
    Revista: ANNALES D ENDOCRINOLOGIE
    ISSN: 0003-4266 Vol.79 N° 2 2018 págs. 85 - 86
  • Autores: Fruhbeck Martínez, Gema; Badimon, L.
    Revista: EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
    ISSN: 0014-2972 Vol.48 N° Supl 1 2018 págs. 6 - 7
  • Autores: Spittal, M. J.; Fruhbeck Martínez, Gema (Autor de correspondencia)
    Revista: LANCET DIABETES AND ENDOCRINOLOGY
    ISSN: 2213-8587 Vol.6 N° 3 2018 págs. 161 - 163
  • Autores: Fruhbeck Martínez, Gema (Autor de correspondencia); Kiortsis, D. N.; Catalán Goñi, Victoria
    Revista: LANCET DIABETES AND ENDOCRINOLOGY
    ISSN: 2213-8587 Vol.6 N° 3 2018 págs. 164 - 166
  • Autores: Unamuno, X.; Fruhbeck Martínez, Gema (Autor de correspondencia)
    Revista: LANCET
    ISSN: 0140-6736 Vol.392 N° 10161 2018 págs. 2239 - 2240
  • Autores: Borras, J. G. (Autor de correspondencia); Escalada San Martín, Francisco Javier; Cases, M. M. ; et al.
    Revista: ENDOCRINOLOGIA DIABETES Y NUTRICION
    ISSN: 2530-0180 Vol.65 N° Supl.1 2018 págs. 1 - 8
  • Autores: Fruhbeck Martínez, Gema; Gómez Ambrosi, Javier; Rodríguez Murueta-Goyena, Amaia; et al.
    Revista: METABOLISM-CLINICAL AND EXPERIMENTAL
    ISSN: 0026-0495 Vol.87 2018 págs. 123 - 135
    Resumen
    Objective: Kallistatin plays an important role in the inhibition of inflammation, oxidative stress, fibrosis and angiogenesis. We aimed to determine the impact of kallistatin on obesity and its associated metabolic alterations as well as its role in adipocyte inflammation and oxidative stress. Methods: Samples obtained from 95 subjects were used in a case-control study. Circulating concentrations and expression levels of kallistatin as well as key inflammation, oxidative stress and extracellular matrix remodelling-related genes were analyzed. Circulating kallistatin concentrations were measured before and after weight loss achieved by Roux-en-Y gastric bypass (RYGB). The impact of kallistatin on lipopolysaccharide (LPS)- and tumour necrosis factor (TNF)-alpha-mediated inflammatory as well as oxidative stress signalling pathways was evaluated. Results: We show that the reduced (P < 0.00001) circulating levels of kallistatin in obese patients increased (P < 0.00001) after RYGB. Moreover, gene expression levels of SERPINA4, the gene coding for kallistatin, were down regulated (P < 0.01) in the liver from obese subjects with non-alcoholic fatty liver disease. Additionally, we revealed that kallistatin reduced (P < 0.05) the expression of inflammation-related genes (CCL2, IL1B, IL6, IL8, TNFA, TGFB) and, conversely, upregulated (P < 0.05) mRNA levels of ADIPOQ and KLF4 in human adipocytes in culture. Kallistatin inhibited (P < 0.05) LPS- and INF-alpha-induced inflammation in human adipocytes via downregulating the expression and secretion of key inflammatory markers. Furthermore, kallistatin also blocked (P < 0.05) TNF-alpha-mediated lipid peroxidation as well as NOX2 and HIF1A expression while stimulating (P < 0.05) the. expression of SIRT1 and FOXO1. Conclusions: These findings provide, for the first time, evidence of a novel role of kallistatin in obesity and its associated comorbidities by limiting adipose tissue inflammation and oxidative stress.
  • Autores: Gomez-Peralta, F. (Autor de correspondencia); Escalada San Martín, Francisco Javier; Torre, E. M.; et al.
    Revista: ENDOCRINOLOGIA DIABETES Y NUTRICION
    ISSN: 2530-0180 Vol.65 N° 10 2018 págs. 611 - 624
    Resumen
    Type 2 diabetes mellitus (DM2) has become a problem of global dimensions by their high and growing prevalence worldwide and the personal and economic costs associated with it. Correct treatment can reduce mortality and associated complications. New concepts have recently been included in routine clinical practice and have changed the algorithm of DM2 pharmacological therapy. Therefore, the Spanish Society of Diabetes (SED) entrusted to the Working Group of Consensus and Clinical Guidelines an update of the 2010 document Recommendations for Pharmacological Treatment of Hyperglycemia in Diabetes type 2. Novel aspects include nine characteristics to describe each drug group: efficiency, the risk of hypoglycemia, effects on body weight, the demonstrated effect in cardiovascular risk, nephroprotection, limitation of use in renal insufficiency, the rate of secondary effects, complexity and costs. Additionally, the document details combination options, and develop the start and adjustment of available injectable therapies. (C) 2018 SEEN y SED. Published by Elsevier Espana, S.L.U. All rights reserved.
  • Autores: Fruhbeck Martínez, Gema; Catalán Goñi, Victoria; Rodríguez Murueta-Goyena, Amaia; et al.
    Revista: ADIPOCYTE
    ISSN: 2162-3945 Vol.7 N° 1 2018 págs. 57 - 62
    Resumen
    Obesity is currently the most extended metabolic disturbance worldwide favoring the development of cardiometabolic alterations such as type 2 diabetes, hypertension, and dyslipidemia. Obesity and the metabolic syndrome (MS) are characterized by an increase in circulating leptin concentrations, in parallel to a decrease in blood levels of adiponectin. Consequently, the adiponectin/leptin ratio has been suggested as a maker of adipose tissue dysfunction. This emerging biomarker correlates with insulin resistance better than adiponectin or leptin alone, or even HOMA and is decreased with increasing number of metabolic risk factors having been proposed as a predictive marker for the MS. Moreover, the adiponectin/leptin ratio is negatively correlated with markers of low-grade chronic inflammation. In this sense, an increase in this ratio has been related with reduced atherosclerosis risk as well as with a decreased risk of some types of cancer in epidemiological studies. In this commentary we propose new cutoffs to estimate obesity- and MS-associated cardiometabolic risk according to the adiponectin/leptin ratio and discuss different therapeutic strategies to increase this promising biomarker of metabolic risk.
  • Autores: Twigg, S. M. (Autor de correspondencia); Escalada San Martín, Francisco Javier; Stella, P. ; et al.
    Revista: DIABETES THERAPY
    ISSN: 1869-6953 Vol.9 N° 5 2018 págs. 2043 - 2053
    Resumen
    To examine the association of baseline patient characteristics with study outcomes in people with type 2 diabetes receiving insulin glargine 300 U/mL (Gla-300) versus glargine 100 U/mL (Gla-100), over a 6-month period. A post hoc patient-level meta-analysis using data from three multicenter, randomized, open-label, parallel-group, phase 3a studies of similar design, in people previously receiving either basal and prandial insulin, basal insulin + oral antihyperglycemic drugs, or no prior insulin (EDITION 1, 2 and 3, respectively). The endpoints, glycated hemoglobin (HbA(1c)), hypoglycemia, body weight change, and insulin dose were investigated by subgroups: age (< 65 and 65 years), body mass index (BMI; < 30 and 30 kg/m(2)), age at onset (< 40, 40-50, and > 50 years), and diabetes duration (< 10 and 10 years). Reduction in HbA(1c) was comparable between insulins, regardless of subgroup. The lower risk of 1 nocturnal (00:00-05:59 h) confirmed ( 3.9 mmol/L [ 70 mg/dL]) or severe hypoglycemic event with Gla-300 versus Gla-100 was also unaffected by participant characteristics. While heterogeneity of treatment effect between diabetes duration subgroups was seen for the risk of 1 confirmed ( 3.9 mmol/L [ 70 mg/dL]) or severe hypoglycemic event at any time (24 h), treatment effect consistently favored Gla-300; no evidence of heterogeneity was observed for the other subgroups. Annualized rates of confirmed ( 3.9 mmol/L [ 70 mg/dL]) or severe hypoglycemia and body weight change were not influenced by participant characteristics; a similar pattern was observed with insulin dose. Comparable glycemic control was observed with Gla-300 versus Gla-100, with less hypoglycemia, regardless of age, BMI, age at onset or diabetes duration. Sanofi. Plain language summary available for this article.
  • Autores: Travez, A.; Rabanal-Ruiz, Y. ; Lopez-Alcala, J. ; et al.
    Revista: JOURNAL OF CELLULAR AND MOLECULAR MEDICINE (ONLINE)
    ISSN: 1582-4934 Vol.22 N° 11 2018 págs. 5648 - 5661
    Resumen
    Adipocyte dysfunction in obesity is commonly associated with impaired insulin signalling in adipocytes and insulin resistance. Insulin signalling has been associated with caveolae, which are coated by large complexes of caveolin and cavin proteins, along with proteins with membrane-binding and remodelling properties. Here, we analysed the regulation and function of a component of caveolae involved in growth factor signalling in neuroendocrine cells, neuroendocrine long coiled-coil protein-2 (NECC2), in adipocytes. Studies in 3T3-L1 cells showed that NECC2 expression increased during adipogenesis. Furthermore, NECC2 co-immunoprecipitated with caveolin-1 (CAV1) and exhibited a distribution pattern similar to that of the components of adipocyte caveolae, CAV1, Cavin1, the insulin receptor and cortical actin. Interestingly, NECC2 overexpression enhanced insulin-activated Akt phosphorylation, whereas NECC2 downregulation impaired insulin-induced phosphorylation of Akt and ERK2. Finally, an up-regulation of NECC2 in subcutaneous and omental adipose tissue was found in association with human obesity and insulin resistance. This effect was also observed in 3T3-L1 adipocytes exposed to hyperglycaemia/hyperinsulinemia. Overall, the present study identifies NECC2 as a component of adipocyte caveolae that is regulated in response to obesity and associated metabolic complications, and supports the contribution of this protein as a molecular scaffold modulating insulin signal transduction at these membrane microdomains.
  • Autores: Álvarez-Cienfuegos Suárez, Francisco Javier; Estevez, M. G.; Ruiz-Canela, Miguel; et al.
    Revista: JOURNAL OF GASTROINTESTINAL SURGERY
    ISSN: 1091-255X Vol.22 N° 4 2018 págs. 713 - 721
    Resumen
    Laparoscopic arcuate ligament release has been demonstrated a valid therapeutic option for arcuate ligament syndrome. Nevertheless, long-term follow-up and predictive factors have not been described for this treatment. Clinical and surgical data and short- and long-term outcomes together with the impact of the degree of stenosis of the celiac trunk were analyzed in 13 consecutive patients who underwent laparoscopic arcuate ligament release between 2001 and 2013. Thirteen patients (12 F/1 M) underwent surgery. The median age was 32 years old, and their mean body mass index was 20.7 (range 14.7-25). The 13 patients presented with intense postprandial abdominal pain. Ten cases were associated with weight loss. The median duration of symptoms was 24 months (range 2-240). Three patients presented symptoms associated with superior mesenteric artery syndrome. Median operative time was 120 min (range 90-240), and there were no conversions to open surgery. Median hospital stay was 3 days (range 2-14). Over a median follow-up of 117 months (range 45-185), nine patients had excellent results although two required endovascular procedures at 70 and 24 months after surgery. Four patients (30.7%) experienced poor outcomes. When we analyzed the impact of the degree of occlusion of the celiac trunk, we observed that in patients with severe occlusion (> 70%), better results were obtained, with complete resolution of symptoms in 71% of cases. Laparoscopic arcuate ligament release constitutes an excellent treatment for arcuate ligament syndrome. The degree of occlusion of the celiac trunk may be a factor predictive of long-term outcomes.
  • Autores: Becerril Mañas, Sara; Rodríguez Murueta-Goyena, Amaia; Catalán Goñi, Victoria; et al.
    Revista: INTERNATIONAL JOURNAL OF OBESITY
    ISSN: 0307-0565 Vol.42 N° 8 2018 págs. 1458 - 1470
    Resumen
    Background/Objectives: Obesity is related to a dynamic extracellular matrix (ECM) remodeling, which involves the synthesis and degradation of different proteins, such as tenascin C (TNC) in the adipose tissue (AT). Given the functional relationship between leptin and inducible nitric oxide synthase (iNOS), our aim was to analyze the impact of the absence of the iNOS gene in AT inflammation and ECM remodeling in ob/ob mice. Subjects/Methods: The expression of genes involved in inflammation and ECM remodeling was evaluated in 10-week-old male double knockout (DBKO) mice simultaneously lacking the ob and iNOS genes as well as in ob/ob mice classified into three groups [control, leptin-treated (1 mg kg(-1) day(-1)) and pair-fed]. Results: Leptin deficiency increased inflammation and fibrosis in AT. As expected, leptin treatment improved the obesity phenotype. iNOS deficiency in ob/ob mice improved insulin sensitivity, AT inflammation, and ECM remodeling, as evidenced by lower AT macrophage infiltration and collagen deposition, a downregulation of proinflammatory and profibrogenic genes Tnf, Emr1, Hif1a, Col6a1, Col6a3, and Tnc, as well as lower circulating TNC levels. Interestingly, leptin upregulated TNC expression and release in 3T3-L1 adipocytes, and iNOS knockdown in 3T3-L1 fat cells produced a significant decrease in basal and leptin-induced Tnc expression. Conclusions: Ablation of iNOS in leptin-deficient mice improved AT inflammation and ECM remodeling-related genes, attenuating fibrosis, and metabolic dysfunction. The activation of iNOS by leptin is necessary for the synthesis and secretion of TNC in adipocytes, suggesting an important role of this alarmin in the development of AT inflammation and fibrosis.
  • Autores: Gómez Ambrosi, Javier (Autor de correspondencia); González Crespo, Ignacio; Catalán Goñi, Victoria; et al.
    Revista: CLINICAL NUTRITION
    ISSN: 0261-5614 Vol.37 N° 2 2018 págs. 580 - 589
    Resumen
    Background & aims: Visceral adipose tissue (VAT) has been shown to be profoundly responsible of most of the obesity-associated metabolic derangements. The measurement of VAT usually implies the use of imaging techniques such as magnetic resonance imaging or computed tomographi(CT), Our aim was to evaluate the accuracy of the determination of VAT by means of abdominal bioimpedance (BIA) with the ViScan device in comparison with Cr and its clinical usefulness in the management of obesity. Methods: We studied a sample of 140 subjects (73 males/67 females) with BMI ranging from 17.7 to 50.4 kg/m(2) to evaluate the accuracy of the ViScan in comparison to CT to determine VAT. To further analyze ViScan's clinical usefulness we studied a separate cohort (n = 2849) analyzing cardiometabolic risk factors. Furthermore, we studied the ability of the ViScan to detect changes in VAT after weight gain (n = 107) or weight loss (n = 335). The study was performed from October 2009 through June 2015. Results: ViScan determines VAT with a good accuracy in individuals with a CT-VAT up to 200 cm(2), and then with lower precision with increasing body mass, exhibiting a moderate high correlation with Cri VAT (r = 0.75, P < 0.001). Importantly, VAT determination with the ViScan exhibits better correlations with several cardiometabolic risk factors such as glucose, triglycerides, HDL-cholesterol and markers of fatty liver than anthropometric measurements such as BMI or waist circumference. ViScan is able to detect VAT variations after body weight changes. Conclusions: Since the possibility of measuring VAT by imaging techniques is not always available, abdominal BIA represents a good alternative to estimate VAT, allowing the identification of patients with increased VAT-related cardiometabolic risk and a better management of obese patients. (C) 2017 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.
  • Autores: Pérez Pevida, Belén; Diaz-Gutierrez, J.; Miras, A. D.; et al.
    Revista: OBESITY
    ISSN: 1930-7381 Vol.26 N° 4 2018 págs. 672 - 682
    Resumen
    ObjectiveThe objective of this study was to assess the utility of the 2-hour oral glucose tolerance test (OGTT) value to discriminate between different cardiometabolic profiles and examine the role of body composition in predicting the associated increased risk for glucose impairment, beta-cell dysfunction, and cardiovascular disease (CVD). MethodsSubjects with normal fasting glucose completed a 2-hour OGTT and were categorized to the carbohydrate metabolism alterations (CMAs) or the control group based on a 2-hour glucose threshold of 7.8 mmol/L. Body composition, visceral adipose tissue, OGTT-based parameters, and cardiovascular risk factors (CVRFs) such as hypertension, dyslipidemia, obstructive sleep apnea, nonalcoholic fatty liver disease, and smoking status were measured. ResultsSubjects with CMAs exhibited a significantly higher 1-hour postload glucose level and a greater decline in beta-cell function and CVRF profiles. After multivariate adjustment, an excess of total body and visceral fat was associated with an increased risk of CMAs, beta-cell dysfunction, CVRFs, and lower whole-body insulin sensitivity. ConclusionsThese data support the etiopathogenic role of body and visceral fat in the development of glucose derangements and CVRFs early on in the metabolic dysregulation process. Thus, body composition analysis and OGTT assessment performed in individuals with normal fasting glucose enable a better identification of patients at risk of developing type 2 diabetes and CVD.
  • Autores: Cheng, Y.; Monteiro, C.; Matos, A.; et al.
    Revista: CLINICAL EPIGENETICS (ONLINE)
    ISSN: 1868-7083 Vol.10 2018 págs. 54
    Resumen
    BACKGROUND: Periprostatic adipose tissue (PPAT) has been recognized to associate with prostate cancer (PCa) aggressiveness and progression. Here, we sought to investigate whether excess adiposity modulates the methylome of PPAT in PCa patients. DNA methylation profiling was performed in PPAT from obese/overweight (OB/OW, BMI¿>¿25 kg m-2) and normal weight (NW, BMI¿<¿25 kg m-2) PCa patients. Significant differences in methylated CpGs between OB/OW and NW groups were inferred by statistical modeling. RESULTS: Five thousand five hundred twenty-six differentially methylated CpGs were identified between OB/OW and NW PCa patients with 90.2% hypermethylated. Four hundred eighty-three of these CpGs were found to be located at both promoters and CpG islands, whereas the representing 412 genes were found to be involved in pluripotency of stem cells, fatty acid metabolism, and many other biological processes; 14 of these genes, particularly FADS1, MOGAT1, and PCYT2, with promoter hypermethylation presented with significantly decreased gene expression in matched samples. Additionally, 38 genes were correlated with antigen processing and presentation of endogenous antigen via MHC class I, which might result in fatty acid accumulation in PPAT and tumor immune evasion. CONCLUSIONS: Results showed that the whole epigenome methylation profiles of PPAT were significantly different in OB/OW compared to normal weight PCa patients. The epigenetic variation associated with excess adiposity likely resulted in altered lipid metabolism and immune dysregulation, contributing towards unfavorable PCa microenvironment, thus warranting further validation studies in larger samples.
  • Autores: Antoñanzas Pérez, Javier; Álvarez-Cienfuegos Suárez, Francisco Javier; Hurtado-Pardo, L.; et al.
    Revista: REVISTA ESPAÑOLA DE ENFERMEDADES DIGESTIVAS
    ISSN: 1130-0108 Vol.110 N° 12 2018 págs. 768 - 774
    Resumen
    Objective: the objective of this study was to analyze the anatomical and clinical features and long-term oncologic outcomes of 25 patients that underwent surgery due to intraductal papillary mucinous neoplasm of the pancreas. Material and methods: patients undergoing surgery for intraductal papillary mucinous neoplasm of the pancreas were identified from a prospective database of pancreatic resections. Demographic data, symptoms, type of surgery and type of lesion (branch type, main duct or mixed) were recorded. The lesions were classified into invasive (high grade dysplasia and carcinoma) and noninvasive (low- or intermediate-grade dysplasia). Postoperative complications were analyzed as well as the pattern of recurrence and disease-free survival at five and ten years. Results: the most common symptoms in the 25 patients (14 males and eleven females) were abdominal pain and weight loss. Eight (32%) cases were diagnosed incidentally. Twelve (48%) of the lesions were of the branch type, three affected the main duct and ten (40%) were mixed. Twelve cephalic duodenopancreatectomies and seven total pancreatectomies were performed; three were central; two, distal; and one, enucleation. Seven cases (32%) had an invasive phenotype. Three patients had locoregional and distant recurrence at six, 16 and 46 months after surgery with a median follow-up of 7.7 years. Disease-free survival at five and ten years for the noninvasive type was 94% and 57% for invasive phenotypes (p < 0.05). Conclusions: intraductal papillary mucinous neoplasm is a heterogeneous entity with well differentiated phenotypes, which requires a tailored strategy and treatment, as established in the current consensus guidelines due to its malignant potential.
  • Autores: Escalada San Martín, Francisco Javier (Autor de correspondencia); Halimi, S.; Senior, P. A. ; et al.
    Revista: DIABETES OBESITY AND METABOLISM
    ISSN: 1462-8902 Vol.20 N° 12 2018 págs. 2860 - 2868
    Resumen
    Aim Materials and Methods To investigate the impact of renal function on the safety and efficacy of insulin glargine 300 U/mL (Gla-300) and insulin glargine 100 U/mL (Gla-100). A meta-analysis was performed using pooled 6-month data from the EDITION 1, 2 and 3 trials (N = 2496). Eligible participants, aged >= 18 years with a diagnosis of type 2 diabetes (T2DM), were randomized to receive once-daily evening injections of Gla-300 or Gla-100. Pooled results were assessed by two renal function subgroups: estimated glomerular filtration rate (eGFR) Results Conclusions The decrease in glycated haemoglobin (HbA1c) after 6 months and the proportion of individuals with T2DM achieving HbA1c targets were similar in the Gla-300 and Gla-100 groups, for both renal function subgroups. There was a reduced risk of nocturnal (12:00-5:59 am) confirmed (<= 3.9 mmol/L [<= 70 mg/dL]) or severe hypoglycaemia with Gla-300 in both renal function subgroups (eGFR <60 mL/min/1.73 m(2): relative risk [RR] 0.76 [95% confidence interval {CI} 0.62-0.94] and eGFR >= 60 mL/min/1.73 m(2): RR 0.75 [95% CI 0.67-0.85]). For confirmed (<= 70 mg/dL [<= 3.9 mmol/L]) or severe hypoglycaemia at any time of day (24 hours) the hypoglycaemia risk was lower with Gla-300 vs Gla-100 in both the lower (RR 0.94 [95% CI 0.86-1.03]) and higher (RR 0.90 [95% CI 0.85-0.95]) eGFR subgroups. Gla-300 provided similar glycaemic control to Gla-100, while indicating a reduced overall risk of confirmed (<= 3.9 and <3.0 mmol/L [<= 70 and <54 mg/dL]) or severe hypoglycaemia, with no significant difference between renal function subgroups.
  • Autores: Burgos-Ramos, E.; Canelles, S. ; Rodríguez Murueta-Goyena, Amaia; et al.
    Revista: MOLECULAR AND CELLULAR ENDOCRINOLOGY
    ISSN: 0303-7207 Vol.470 2018 págs. 48 - 59
    Resumen
    Insulin potentiates leptin effects on muscle accrual and glucose homeostasis. However, the relationship between leptin's central effects on peripheral insulin sensitivity and the associated structural changes remain unclear. We hypothesized that central leptin infusion modifies muscle size through activation of insulin signaling. Muscle insulin signaling, enzymes of fatty acid metabolism, mitochondrial respiratory chain complexes, proliferating cell nuclear antigen (PCNA) and fiber area were analyzed in the gastrocnemius of chronic central infused (L), pair-fed (PF) and control rats. PCNA-positive nuclei, fiber area, GLUT4 and glycogen levels and activation of Akt and mechanistic target of rapamycin were increased in L with no changes in PF. Acetyl-CoA carboxylase-beta mRNA levels and non-esterified fatty acid and triglyceride content were reduced and carnitine palmitoyltransferase-lb expression and mitochondrial complexes augmented in L These results suggest that leptin promotes an increase in muscle size associated with improved insulin signaling favored by lipid profile. (C) 2017 Elsevier B.V. All rights reserved.
  • Autores: Moreno-Navarrete, J. M.; Rodríguez Murueta-Goyena, Amaia; Becerril Mañas, Sara; et al.
    Revista: MOLECULAR NUTRITION AND FOOD RESEARCH
    ISSN: 1613-4125 Vol.62 N° 2 2018
    Resumen
    Scope: To investigate intestinal markers of iron absorption in morbidly obese subjects according to glucose tolerance. Methods and results: Gene expression of both non-heme (SLC40A1 (ferroportin), SLC11A2) and heme iron (SLC46A1 (HCP1), HMOX1) transporters is analyzed in 38 small intestine tissue samples [11 with normal glucose tolerance, 14 with glucose intolerance (GI), and 13 with newly diagnosed type 2 diabetes (T2D)]. SLC40A1 (r = 0.43, p = 0.008) and SLC11A2 (r = 0.35, p = 0.03) mRNA levels are positively correlated with ferritin-to-hepcidin ratio and with fasting glucose, being significantly increased in patients with T2D. Only ferroportin is negatively associated with serum hepcidin (r = -0.617, p < 0.0001). In multivariate regression analysis, fasting glucose contributes independently to intestinal SLC40A1 (p = 0.009) and SLC11A2 (p = 0.04) variance after controlling for age, sex, and BMI. When circulating hepcidin is incorporated into the model, fasting glucose contributes significantly and independently to intestinal SLC40A1 (p = 0.02), but not to SLC11A2 (p = 0.07) variance. SLC46A1 and HMOX1 are similar in all groups. Conclusion: The expression of ferroportin and SLC11A2 is increased in the intestine of patients with T2D in association with iron stores and serum hepcidin levels. Increased intestinal iron absorption is a potential mechanism that could explain the increased body iron stores frequently observed in patients with T2D.
  • Autores: Ortega, F. J.; Moreno-Navarrete, J. M.; Mercader, J. M.; et al.
    Revista: EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
    ISSN: 0014-2972 Vol.48 N° Supl 1 2018 págs. 67
  • Autores: Tuero Ojanguren, Carlota; Granero Peiro, Lucia; Rotellar Sastre, Fernando; et al.
    Revista: EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
    ISSN: 0014-2972 Vol.48 N° Supl 1 2018 págs. 202
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    Revista: EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
    ISSN: 0014-2972 Vol.48 N° Supl. 1 2018 págs. 191 - 192
  • Autores: Tuero Ojanguren, Carlota; Granero Peiro, Lucia; Ahechu Garayoa, Patricia; et al.
    Revista: EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
    ISSN: 0014-2972 Vol.48 N° Supl 1 2018 págs. 202
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    Revista: EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
    ISSN: 0014-2972 Vol.48 N° Supl. 1 2018 págs. 210 - 211
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    Revista: EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
    ISSN: 0014-2972 Vol.48 N° Supl.1 2018 págs. 193 - 194
  • Autores: Tuero Ojanguren, Carlota; Ahechu Garayoa, Patricia; Rotellar Sastre, Fernando; et al.
    Revista: EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
    ISSN: 0014-2972 Vol.48 N° Supl 1 2018 págs. 203
  • Autores: Escalada San Martín, Francisco Javier; Bonnet, F.; Wu, J. ; et al.
    Revista: VALUE IN HEALTH
    ISSN: 1098-3015 Vol.21 N° Supl. 3 2018 págs. S120 - S120
  • Autores: Ibáñez Solano, Patricia; Vila, N. ; Santesteban, V.; et al.
    Revista: EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
    ISSN: 0014-2972 Vol.48 N° Supl. 1 2018 págs. 192
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